Acetic acid amide derivative having inhibitory activity on endothelial lipase

ABSTRACT

Disclosed is a compound which is useful as an endothelial lipase inhibitor. 
     A pharmaceutical composition having inhibitory activity on endothelial lipase comprising a compound represented by the formula: 
     
       
         
         
             
             
         
       
     
     its pharmaceutically acceptable salt, or a solvate thereof,
 
wherein
         Ring A is nitrogen-containing hetero ring,   Ring A may be substituted with a substituent other than a group represented by the formula: —C(R 1 R 2 )—C(═O)—NR 3 R 4  and a group represented by the formula: —R 5 ,   a broken line represents the presence or the absence of a bond,   Z is —NR 6 —, ═N—, —O—, or —S—,   R 6  is halogen, substituted or unsubstituted alkyl or the like,   R 1  and R 2  are each independently hydrogen, halogen, hydroxy, cyano, nitro, carboxy or substituted or unsubstituted alkyl,   R 3  is hydrogen or substituted or unsubstituted alkyl,   R 4  is hydrogen, substituted or unsubstituted alkyl or the like,   R 3  and R 4  taken together with the adjacent nitrogen atom to which they are attached may form a substituted or unsubstituted ring,   R 5  is hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl or the like.

FIELD OF THE INVENTION

The present invention relates to a pharmaceutically useful compoundhaving inhibitory activity on endothelial lipase (hereinafter, referredto as EL).

BACKGROUND ART

Endothelial Lipase (EL) is a Triglyceride Lipase family on a par withLipoprotein Lipase (LPL) and Hepatic Lipase (HL). Studies in theknockout mouse and transgenic mouse have indicated that EndothelialLipase (EL) is associated with the metabolism of HDLc by the strongphospholipase activity, and Endothelial Lipase (EL) is accepted as afactor which regulates plasma HDLc levels (Non-Patent Document 1).

Plasma HDLc levels are accepted as an inverse correlate of coronaryartery disease (CAD) risk. HDLc is supposed that ananti-arteriosclerosis action is shown through an anti-oxidizationaction, an antiinflammatory effect, a cholesterol reverse transmissionaction or the like, and low HDLc levels are accepted as one of therisk-factors of CAD.

Therefore, an EL inhibitor serves as a CAD therapeutic agent through theincrease of HDLc, and increase of a HDLc and reduction of anarteriosclerosis pathological change part is reported by studies in ELknockout clinical mouse (Non-Patent Document 2).

These facts suggest the possibility of a selective inhibitor of EL as atherapeutic agent in lipid metabolism abnormality and arteriosclerosis.

Patent Document 1, 2 and 3 disclose various compounds having inhibitoryactivity on hepatic lipase and/or endothelial lipase, but acetic acidamide derivative such as the present compound has not been disclosed.

Patent Document 4 discloses a compound having inhibitory activity ontriglyceride lipase, lipoprotein lipase, hepatic lipase, pancreaticlipase or endothelial lipase, but acetic acid amide derivative such asthe present compound has not been disclosed.

Patent Document 5 to 13 disclose various compounds having inhibitoryactivity on EL, but acetic acid amide derivative such as the presentcompound has not been disclosed.

Patent Document 14 discloses a compound having inhibitory activity onMIF (Macrophage Migration Inhibitory Factor), but does not describe theinhibitory activity on EL and the increasing activity of HDLc.

Patent Document 15 discloses a derivative in which 2-position ofbenzothiazole or benzoxazole is substituted with acetic acid amide groupas a compound useful for sleep disorders, but does not describe theinhibitory activity on EL.

PRIOR ART DOCUMENT Patent Document

-   [Patent Document 1] WO2004/093872-   [Patent Document 2] WO2004/094393-   [Patent Document 3] WO2004/094394-   [Patent Document 4] WO2006/053250-   [Patent Document 5] WO2007/042178-   [Patent Document 6] WO2007/045392-   [Patent Document 7] WO2007/045393-   [Patent Document 8] WO2007/110216-   [Patent Document 9] WO2007/110215-   [Patent Document 10] WO2007/131231-   [Patent Document 11] WO2007/131232-   [Patent Document 12] WO2007/131233-   [Patent Document 13] WO2006/111321 pamphlet-   [Patent Document 14] JP2001-097979-   [Patent Document 15] FR2904973

Non-Patent Document

-   [Non-Patent Document 1]TCM, Vol. 14, No. 5, 2004, p. 202-206-   [Non-Patent Document 2]The Journal of Biological Chemistry Vol. 279,    No. 43, Issue of Oct. 22, 45085-45092, 2004

DISCLOSURE OF INVENTION Problems to be Solved by the Invention

The present invention provides a useful endothelial lipase inhibitor.

Means to Solve the Problems

The present inventors have intensively studied to synthesize theexcellent compounds having inhibitory activity on endothelial lipase.

The present invention includes:

(1)

A pharmaceutical composition having inhibitory activity on endotheliallipase comprising a compound represented by the formula (I):

its pharmaceutically acceptable salt, or a solvate thereof,wherein

Ring A is nitrogen-containing hetero ring,

Ring A may be substituted with a substituent other than a grouprepresented by the formula: —C(R¹R²)—C(═O)—NR³R⁴ and a group representedby the formula: —R⁵,

a broken line represents the presence or the absence of a bond,

Z is —NR⁶, —N—, —O—, or —S—,

R⁶ is hydrogen, substituted or unsubstituted alkyl, substituted orunsubstituted alkenyl, substituted or unsubstituted alkynyl, substitutedor unsubstituted aryl, substituted or unsubstituted heteroaryl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedcycloalkenyl or substituted or unsubstituted heterocycle,

R¹ and R² are each independently hydrogen, halogen, cyano, nitro,carboxy or substituted or unsubstituted alkyl,

R³ is hydrogen or substituted or unsubstituted alkyl,

R⁴ is hydrogen, substituted or unsubstituted alkyl, substituted orunsubstituted alkenyl, substituted or unsubstituted alkynyl, substitutedor unsubstituted aryl, substituted or unsubstituted heteroaryl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedcycloalkenyl, substituted or unsubstituted heterocycle or substituted orunsubstituted amino,

R³ and R⁴ taken together with the adjacent nitrogen atom to which theyare attached may form a substituted or unsubstituted ring,

R⁵ is hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted orunsubstituted alkyl, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkyloxy, substituted orunsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted cycloalkyloxy, substituted or unsubstitutedcycloalkenyloxy, substituted or unsubstituted heterocycleoxy,substituted or unsubstituted alkylthio, substituted or unsubstitutedarylthio, substituted or unsubstituted heteroarylthio, substituted orunsubstituted cycloalkylthio, substituted or unsubstitutedcycloalkenylthio, substituted or unsubstituted heterocyclethio,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedarylsulfonyl, substituted or unsubstituted heteroarylsulfonyl,substituted or unsubstituted cycloalkylsulfonyl, substituted orunsubstituted cycloalkenylsulfonyl, substituted or unsubstitutedheterocyclesulfonyl, substituted or unsubstituted acyl, substituted orunsubstituted carbamoyl or substituted or unsubstituted amino,

with the proviso that compounds wherein Ring A is thiazolopyrimidine andR³ and R⁴ taken together with the adjacent nitrogen atom to which theyare attached may form a substituted or unsubstituted ring are excluded,

(2)

The pharmaceutical composition having inhibitory activity on endotheliallipase comprising the compound according to the above (1), itspharmaceutically acceptable salt, or a solvate thereof, wherein Z is—S—,

(3)

The pharmaceutical composition having inhibitory activity on endotheliallipase comprising the compound according to the above (1) or (2), itspharmaceutically acceptable salt, or a solvate thereof, wherein Ring Ais monocyclic nitrogen-containing aromatic hetero ring,

(4)

The pharmaceutical composition having inhibitory activity on endotheliallipase comprising the compound according to the above (1) or (2), itspharmaceutically acceptable salt, or a solvate thereof, wherein Ring Ais bicyclic nitrogen-containing aromatic hetero ring,

(5)

The pharmaceutical composition having inhibitory activity on endotheliallipase comprising the compound according to any one of the above (1) to(4), its pharmaceutically acceptable salt, or a solvate thereof, whereinR⁵ is substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl, substituted or unsubstituted heterocycle,substituted or unsubstituted aryloxy, substituted or unsubstitutedheteroaryloxy, substituted or unsubstituted cycloalkyloxy, substitutedor unsubstituted cycloalkenyloxy, substituted or unsubstitutedheterocycleoxy, substituted or unsubstituted arylthio, substituted orunsubstituted heteroarylthio, substituted or unsubstitutedcycloalkylthio, substituted or unsubstituted cycloalkenylthio,substituted or unsubstituted heterocyclethio, substituted orunsubstituted arylsulfonyl, substituted or unsubstitutedheteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl,substituted or unsubstituted cycloalkenylsulfonyl, substituted orunsubstituted heterocyclesulfonyl or substituted or unsubstituted amino,

(6)

The pharmaceutical composition having inhibitory activity on endotheliallipase comprising the compound according to any one of the above (1) to(5), its pharmaceutically acceptable salt, or a solvate thereof, whereinR⁵ is substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted aryloxy, substituted orunsubstituted heteroaryloxy, substituted or unsubstituted arylthio,substituted or unsubstituted heteroarylthio, substituted orunsubstituted arylsulfonyl, substituted or unsubstitutedheteroarylsulfonyl or substituted or unsubstituted amino,

(7)

The pharmaceutical composition having inhibitory activity on endotheliallipase comprising the compound according to any one of the above (1) to(6), its pharmaceutically acceptable salt, or a solvate thereof, whereinR⁴ is substituted or unsubstituted alkyl, wherein substituted orunsubstituted alkyl is substituted or unsubstituted arylalkyl orsubstituted or unsubstituted heteroarylalkyl,

(8)

A compound represented by the formula (II):

its pharmaceutically acceptable salt, or a solvate thereof,wherein

Z¹ is —O— or —S—,

Ring B is aromatic carbocycle, aromatic hetero ring, nonaromaticcarbocycle or nonaromatic hetero ring,

R¹ and R² are each independently hydrogen, halogen, cyano, nitro,carboxy or substituted or unsubstituted alkyl,

R³ is hydrogen or substituted or unsubstituted alkyl,

R^(4a) is substituted or unsubstituted arylalkyl, substituted orunsubstituted heteroarylalkyl, substituted or unsubstitutedcycloalkylalkyl, substituted or unsubstituted cycloalkenylalkyl,substituted or unsubstituted heterocyclealkyl,

a group represented by the formula: —(CR⁷R⁸)n-C(═O)—R⁹, wherein R⁷ andR⁸ are each independently hydrogen, halogen, hydroxy, carboxy,substituted or unsubstituted alkyl, substituted or unsubstitutedalkyloxy, substituted or unsubstituted aryl, substituted orunsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl or substituted orunsubstituted heterocycle, n is an integer of 1 to 10, R⁹ is —OR¹⁰ or—NR¹¹R¹², R¹⁰ is hydrogen, substituted or unsubstituted alkyl,substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl or substituted or unsubstituted heterocycle,R¹¹ and R¹² are each independently hydrogen, substituted orunsubstituted alkyl, substituted or unsubstituted alkyloxy, substitutedor unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedaryl, substituted or unsubstituted heteroaryl, substituted orunsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl orsubstituted or unsubstituted heterocycle or

a group represented by the formula: —C(R⁷R⁸)n-O—R¹³, wherein R⁷, R⁸ andn are as defined in the above, R¹³ is hydrogen or substituted orunsubstituted alkyl,

R³ and R^(4a) taken together with the adjacent nitrogen atom to whichthey are attached may form a substituted or unsubstituted ring,

R⁵ is hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted orunsubstituted alkyl, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkyloxy, substituted orunsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted cycloalkyloxy, substituted or unsubstitutedcycloalkenyloxy, substituted or unsubstituted heterocycleoxy,substituted or unsubstituted alkylthio, substituted or unsubstitutedarylthio, substituted or unsubstituted heteroarylthio, substituted orunsubstituted cycloalkylthio, substituted or unsubstitutedcycloalkenylthio, substituted or unsubstituted heterocyclethio,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedarylsulfonyl, substituted or unsubstituted heteroarylsulfonyl,substituted or unsubstituted cycloalkylsulfonyl, substituted orunsubstituted cycloalkenylsulfonyl, substituted or unsubstitutedheterocyclesulfonyl, substituted or unsubstituted acyl, substituted orunsubstituted carbamoyl or substituted or unsubstituted amino,

R^(X) is halogen, hydroxy, cyano, nitro, carboxy, substituted orunsubstituted alkyl, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkyloxy, substituted orunsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted cycloalkyloxy, substituted or unsubstitutedcycloalkenyloxy, substituted or unsubstituted heterocycleoxy,substituted or unsubstituted alkylthio, substituted or unsubstitutedarylthio, substituted or unsubstituted heteroarylthio, substituted orunsubstituted cycloalkylthio, substituted or unsubstitutedcycloalkenylthio, substituted or unsubstituted heterocyclethio,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedarylsulfonyl, substituted or unsubstituted heteroarylsulfonyl,substituted or unsubstituted cycloalkylsulfonyl, substituted orunsubstituted cycloalkenylsulfonyl, substituted or unsubstitutedheterocyclesulfonyl, substituted or unsubstituted acyl, substituted orunsubstituted carbamoyl or substituted or unsubstituted amino,

m is an integer of 0 to 3,

with the proviso that compounds, wherein Z¹ is —S—, Ring B is pyrimidineand R³ and R^(4a) taken together with the adjacent nitrogen atom towhich they are attached may form a substituted or unsubstituted ring,compounds, wherein Z¹ is —O—, Ring B is benzene, R⁵ is methyl, m is 0and R³ and R^(4a) taken together with the adjacent nitrogen atom towhich they are attached may form a substituted or unsubstituted ring,compounds, wherein Z¹ is —O—, Ring B is benzene, R⁵ is hydrogen, m is 1,R^(X) is methyl, and R³ and R^(4a) taken together with the adjacentnitrogen atom to which they are attached may form a substituted orunsubstituted ring and the compounds shown as follows are excluded:

(9)

The compound according to the above (8), its pharmaceutically acceptablesalt, or a solvate thereof, wherein Z¹ is —S—,

(10)

The compound according to the above (8) or (9), its pharmaceuticallyacceptable salt, or a solvate thereof, wherein Ring B is aromaticcarbocycle,

(11)

The compound according to any one of the above (8) to (10), itspharmaceutically acceptable salt, or a solvate thereof, wherein Ring Bis benzene,

(12)

The compound according to the above (8) or (9), its pharmaceuticallyacceptable salt, or a solvate thereof, wherein Ring B is monocyclicaromatic hetero ring,

(13)

The compound according to any one of the above (9) to (12), itspharmaceutically acceptable salt, or a solvate thereof, wherein thecompound represented by the formula (II) is a compound represented bythe formula (III):

wherein X and Y are each independently —CR^(X)═, —CH═, or —N═, R^(Y) ishydrogen or R^(X), R¹, R², R³, R^(4a), R⁵ and R^(X) are as defined inthe above (8),(14)

The compound according to any one of the above (9) to (12), itspharmaceutically acceptable salt, or a solvate thereof, wherein thecompound represented by the formula (II) is a compound represented bythe formula (IV):

wherein X and Y are each independently —CR^(X)═, —CH═, or —N═, R^(Y) ishydrogen or R^(X), R¹, R², R³, R^(4a), R⁵ and R^(X) are as defined inthe above (8),(15)

The compound according to the above (13) or (14), its pharmaceuticallyacceptable salt, or a solvate thereof, wherein X and Y are eachindependently —CR^(X)═ or —CH═,

(16)

The compound according to any one of the above (8) to (15), itspharmaceutically acceptable salt, or a solvate thereof, wherein R^(4a)is substituted or unsubstituted arylalkyl or substituted orunsubstituted heteroarylalkyl,

(17)

The compound according to any one of the above (8) to (16), itspharmaceutically acceptable salt, or a solvate thereof, wherein R^(4a)is substituted or unsubstituted arylalkyl,

(18)

The compound according to any one of the above (8) to (16), itspharmaceutically acceptable salt, or a solvate thereof, wherein R^(4a)is

wherein R^(a) is halogen, hydroxy, carboxy, nitro, cyano, azide,substituted or unsubstituted alkyl, substituted or unsubstitutedalkenyl, substituted or unsubstituted alkynyl, substituted orunsubstituted aryl, substituted or unsubstituted cycloalkyl, substitutedor unsubstituted cycloalkenyl, substituted or unsubstituted heteroaryl,substituted or unsubstituted heterocycle, substituted or unsubstitutedalkyloxy, substituted or unsubstituted aryloxy, substituted orunsubstituted silyloxy, substituted or unsubstituted amino, substitutedor unsubstituted carbamoyl, substituted or unsubstituted carbamoyloxy,substituted or unsubstituted acyl, substituted or unsubstitutedalkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted orunsubstituted sulfamoyl or substituted or unsubstitutedalkyloxycarbonyl, R¹⁴ and R¹⁵ are each independently hydrogen, halogen,hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl,substituted or unsubstituted alkenyl or substituted or unsubstitutedalkynyl, b is an integer of 0 to 3,(19)

The compound according to the above (18), its pharmaceuticallyacceptable salt, or a solvate thereof, wherein R^(4a) is

wherein R^(a), R¹⁴ and R¹⁵ are as defined in the above (18), c is aninteger of 0 to 2,(20)

The compound according to any one of the above (8) to (15), itspharmaceutically acceptable salt, or a solvate thereof, wherein R^(4a)is a group represented by the formula: —(CR⁷R⁸)n-C(═O)—R⁹, wherein R⁷,R⁸, R⁹ and n are as defined in the above (8),

(21)

The compound according to the above (20), its pharmaceuticallyacceptable salt, or a solvate thereof, wherein R⁹ is —OR¹⁰,

(22)

The compound according to the above (20), its pharmaceuticallyacceptable salt, or a solvate thereof, wherein R⁹ is —NR¹¹R¹²,

(23)

The compound according to the above (22), its pharmaceuticallyacceptable salt, or a solvate thereof, wherein R¹² is substituted orunsubstituted alkyl,

(24)

The compound according to the above (22) or (23), its pharmaceuticallyacceptable salt, or a solvate thereof, wherein R¹¹ is hydrogen,

(25)

The compound according to any one of the above (20) to (24), itspharmaceutically acceptable salt, or a solvate thereof, wherein n is 1,

(26)

The compound according to any one of the above (20) to (25), itspharmaceutically acceptable salt, or a solvate thereof, wherein R⁷ andR⁸ are hydrogen,

(27)

The compound according to any one of the above (8) to (26), itspharmaceutically acceptable salt, or a solvate thereof, wherein R¹ andR² are hydrogen,

(28)

The compound according to any one of the above (8) to (27), itspharmaceutically acceptable salt, or a solvate thereof, wherein R³ ishydrogen,

(29)

The compound according to any one of the above (8) to (28), itspharmaceutically acceptable salt, or a solvate thereof, wherein R⁵ issubstituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl, substituted or unsubstituted heterocycle,substituted or unsubstituted aryloxy, substituted or unsubstitutedheteroaryloxy, substituted or unsubstituted cycloalkyloxy, substitutedor unsubstituted cycloalkenyloxy, substituted or unsubstitutedheterocycleoxy, substituted or unsubstituted arylthio, substituted orunsubstituted heteroarylthio, substituted or unsubstitutedcycloalkylthio, substituted or unsubstituted cycloalkenylthio,substituted or unsubstituted heterocyclethio, substituted orunsubstituted arylsulfonyl, substituted or unsubstitutedheteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl,substituted or unsubstituted cycloalkenylsulfonyl, substituted orunsubstituted heterocyclesulfonyl or substituted or unsubstituted amino,

(30)

The compound according to any one of the above (8) to (29), itspharmaceutically acceptable salt, or a solvate thereof, wherein R⁵ issubstituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted aryloxy, substituted orunsubstituted heteroaryloxy, substituted or unsubstituted arylthio,substituted or unsubstituted heteroarylthio, substituted orunsubstituted arylsulfonyl, substituted or unsubstitutedheteroarylsulfonyl or substituted or unsubstituted amino,

(31)

The compound according to any one of the above (8) to (28), itspharmaceutically acceptable salt, or a solvate thereof, wherein R⁵ ishydrogen, substituted or unsubstituted alkyl, substituted orunsubstituted alkenyl, substituted or unsubstituted alkynyl, substitutedor unsubstituted aryl, substituted or unsubstituted heteroaryl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkyloxy, substituted orunsubstituted aryloxy, substituted or unsubstituted arylsulfonyl orsubstituted or unsubstituted acyl,

(32)

A compound represented by the formula (V):

its pharmaceutically acceptable salt, or a solvate thereof,wherein

Ring C is monocyclic or bicyclic hetero ring,

R^(4b) is substituted arylalkyl, wherein a substituent on a ring of thesubstituted arylalkyl is carboxy, substituted or unsubstitutedcarbamoyl, substituted or unsubstituted alkylsulfonyl or substituted orunsubstituted sulfamoyl, substituted heteroarylalkyl, wherein asubstituent on a ring of the substituted heteroarylalkyl is carboxy,substituted or unsubstituted carbamoyl, substituted or unsubstitutedalkylsulfonyl or substituted or unsubstituted sulfamoyl, substitutedcycloalkylalkyl, wherein a substituent on a ring of the substitutedcycloalkylalkyl is carboxy, substituted or unsubstituted carbamoyl,substituted or unsubstituted alkylsulfonyl or substituted orunsubstituted sulfamoyl, substituted cycloalkenylalkyl, wherein asubstituent on a ring of the substituted cycloalkenylalkyl is carboxy,substituted or unsubstituted carbamoyl, substituted or unsubstitutedalkylsulfonyl or substituted or unsubstituted sulfamoyl, substitutedheterocyclealkyl, wherein a substituent on a ring of the substitutedheterocyclealkyl is carboxy, substituted or unsubstituted carbamoyl,substituted or unsubstituted alkylsulfonyl or substituted orunsubstituted sulfamoyl or

a group represented by the formula: —(CR⁷R⁸)n-C(═O)—R⁹, wherein R⁷ andR⁸ are each independently hydrogen, halogen, hydroxy, carboxy,substituted or unsubstituted alkyl, substituted or unsubstitutedalkyloxy, substituted or unsubstituted aryl, substituted orunsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl or substituted orunsubstituted heterocycle, n is an integer of 1 to 10, R⁹ is —OR¹⁰ or—NR¹¹R¹², R¹⁰ is hydrogen, substituted or unsubstituted alkyl,substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl or substituted or unsubstituted heterocycle,R¹¹ and R¹² are each independently hydrogen, substituted orunsubstituted alkyl, substituted or unsubstituted alkyloxy, substitutedor unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedaryl, substituted or unsubstituted heteroaryl, substituted orunsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl orsubstituted or unsubstituted heterocycle,

R⁵ is hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted orunsubstituted alkyl, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkyloxy, substituted orunsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted cycloalkyloxy, substituted or unsubstitutedcycloalkenyloxy, substituted or unsubstituted heterocycleoxy,substituted or unsubstituted alkylthio, substituted or unsubstitutedarylthio, substituted or unsubstituted heteroarylthio, substituted orunsubstituted cycloalkylthio, substituted or unsubstitutedcycloalkenylthio, substituted or unsubstituted heterocyclethio,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedarylsulfonyl, substituted or unsubstituted heteroarylsulfonyl,substituted or unsubstituted cycloalkylsulfonyl, substituted orunsubstituted cycloalkenylsulfonyl, substituted or unsubstitutedheterocyclesulfonyl, substituted or unsubstituted acyl, substituted orunsubstituted carbamoyl or substituted or unsubstituted amino,

R^(X) is halogen, hydroxy, cyano, nitro, carboxy, substituted orunsubstituted alkyl, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkyloxy, substituted orunsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted cycloalkyloxy, substituted or unsubstitutedcycloalkenyloxy, substituted or unsubstituted heterocycleoxy,substituted or unsubstituted alkylthio, substituted or unsubstitutedarylthio, substituted or unsubstituted heteroarylthio, substituted orunsubstituted cycloalkylthio, substituted or unsubstitutedcycloalkenylthio, substituted or unsubstituted heterocyclethio,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedarylsulfonyl, substituted or unsubstituted heteroarylsulfonyl,substituted or unsubstituted cycloalkylsulfonyl, substituted orunsubstituted cycloalkenylsulfonyl, substituted or unsubstitutedheterocyclesulfonyl, substituted or unsubstituted acyl, substituted orunsubstituted carbamoyl or substituted or unsubstituted amino,

m is an integer of 0 to 3,

with the proviso that the compounds shown as follows are excluded:

(33)

The compound according to the above (32), its pharmaceuticallyacceptable salt, or a solvate thereof, wherein Ring C is bicycle,

(34)

A pharmaceutical composition comprising the compound according to anyone of the above (8) to (33), its pharmaceutically acceptable salt, or asolvate thereof,

(35)

A pharmaceutical composition comprising the compound according to anyone of the above (8) to (33), its pharmaceutically acceptable salt, or asolvate thereof, which has an inhibitory activity on endothelial lipase,

(36)

The pharmaceutical composition according to any one of the above (1) to(7) or (34) for treating and/or preventing lipid metabolism abnormality,

(37)

The pharmaceutical composition according to any one of the above (1) to(7) or (34) for treating and/or preventing hyperlipidemia,

(38)

The pharmaceutical composition according to any one of the above (1) to(7) or (34) for treating and/or preventing arteriosclerosis,

(39)

A method for preventing or treating lipid metabolism abnormality,comprising administering the compound according to any one of the above(1) to (33), its pharmaceutically acceptable salt, or a solvate thereof,

(40)

A method for preventing or treating hyperlipidemia, comprisingadministering the compound according to any one of the above (1) to(33), its pharmaceutically acceptable salt, or a solvate thereof,

(41)

A method for preventing or treating arteriosclerosis, comprisingadministering the compound according to any one of the above (1) to(33), its pharmaceutically acceptable salt, or a solvate thereof,

(42)

A use of the compound according to any one of the above (1) to (33), itspharmaceutically acceptable salt, or a solvate thereof for manufacturinga medicament of treatment and/or prevention of lipid metabolismabnormality,

(43)

A use of the compound according to any one of the above (1) to (33), itspharmaceutically acceptable salt, or a solvate thereof for manufacturinga medicament of treatment and/or prevention of hyperlipidemia,

(44)

A use of the compound according to any one of the above (1) to (33), itspharmaceutically acceptable salt, or a solvate thereof for manufacturinga medicament of treatment and/or prevention of arteriosclerosis,

(45)

The compound according to any one of the above (1) to (33), itspharmaceutically acceptable salt, or a solvate thereof for the treatmentand/or prevention of lipid metabolism abnormality,

(46)

The compound according to any one of the above (1) to (33), itspharmaceutically acceptable salt, or a solvate thereof for the treatmentand/or prevention of hyperlipidemia,

(47)

The compound according to any one of the above (1) to (33), itspharmaceutically acceptable salt, or a solvate thereof for the treatmentand/or prevention of arteriosclerosis.

Further, the present invention includes:

(A1)

A pharmaceutical composition having inhibitory activity on endotheliallipase comprising a compound represented by the formula (I):

its pharmaceutically acceptable salt, or a solvate thereof,wherein

Ring A is nitrogen-containing hetero ring,

Ring A may be substituted with a substituent other than a grouprepresented by the formula: —C(R¹R²)—C(═O)—NR³R⁴ and a group representedby the formula: —R⁵,

a broken line represents the presence or the absence of a bond,

Z is —NR⁶—, ═N—, —O—, or —S—,

R⁶ is hydrogen, substituted or unsubstituted alkyl, substituted orunsubstituted alkenyl, substituted or unsubstituted alkynyl, substitutedor unsubstituted aryl, substituted or unsubstituted heteroaryl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedcycloalkenyl or substituted or unsubstituted heterocycle,

R¹ and R² are each independently hydrogen, halogen, hydroxy, cyano,nitro, carboxy or substituted or unsubstituted alkyl,

R³ is hydrogen or substituted or unsubstituted alkyl,

R⁴ is hydrogen, substituted or unsubstituted alkyl, substituted orunsubstituted alkenyl, substituted or unsubstituted alkynyl, substitutedor unsubstituted aryl, substituted or unsubstituted heteroaryl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedcycloalkenyl, substituted or unsubstituted heterocycle or substituted orunsubstituted amino,

R³ and R⁴ taken together with the adjacent nitrogen atom to which theyare attached may form a substituted or unsubstituted ring,

R⁵ is hydrogen, substituted or unsubstituted alkyl, substituted orunsubstituted alkenyl, substituted or unsubstituted alkynyl, substitutedor unsubstituted aryl, substituted or unsubstituted heteroaryl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedcycloalkenyl, substituted or unsubstituted heterocycle, substituted orunsubstituted alkyloxy, substituted or unsubstituted cycloalkyloxy,substituted or unsubstituted aryloxy, substituted or unsubstitutedheteroaryloxy, substituted or unsubstituted heterocycleoxy, substitutedor unsubstituted alkylthio, substituted or unsubstituted cycloalkylthio,substituted or unsubstituted cycloalkenylthio, substituted orunsubstituted arylthio, substituted or unsubstituted heteroarylthio,substituted or unsubstituted heterocyclethio, substituted orunsubstituted alkylsulfonyl, substituted or unsubstitutedcycloalkylsulfonyl, substituted or unsubstituted cycloalkenylsulfonyl,substituted or unsubstituted arylsulfonyl, substituted or unsubstitutedheteroarylsulfonyl, substituted or unsubstituted heterocyclesulfonyl,substituted or unsubstituted acyl or substituted or unsubstituted amino,

(A2)

The pharmaceutical composition having inhibitory activity on endotheliallipase comprising the compound according to the above (A1), itspharmaceutically acceptable salt, or a solvate thereof, wherein Z is—S—,

(A3)

The pharmaceutical composition having inhibitory activity on endotheliallipase comprising the compound according to the above (A1) or (A2), itspharmaceutically acceptable salt, or a solvate thereof, wherein Ring Ais monocyclic nitrogen-containing aromatic hetero ring,

(A4)

The pharmaceutical composition having inhibitory activity on endotheliallipase comprising the compound according to the above (A1) or (A2), itspharmaceutically acceptable salt, or a solvate thereof, wherein Ring Ais bicyclic nitrogen-containing aromatic hetero ring,

(A5)

The pharmaceutical composition having inhibitory activity on endotheliallipase comprising the compound according to any one of the above (A1) to(A4), its pharmaceutically acceptable salt, or a solvate thereof,wherein R⁴ is substituted or unsubstituted alkyl, wherein substituted orunsubstituted alkyl is substituted or unsubstituted arylalkyl orsubstituted or unsubstituted heteroarylalkyl,

(A6)

A compound represented by the formula (II):

its pharmaceutically acceptable salt, or a solvate thereof,wherein

Z¹ is —O— or —S—,

Ring B is aromatic carbocycle, aromatic hetero ring, nonaromaticcarbocycle or nonaromatic hetero ring,

R¹ and R² are each independently hydrogen, halogen, hydroxy, cyano,nitro, carboxy or substituted or unsubstituted alkyl,

R³ is hydrogen or substituted or unsubstituted alkyl,

R^(4a) is substituted or unsubstituted arylalkyl, substituted orunsubstituted heteroarylalkyl, substituted or unsubstitutedcycloalkylalkyl, substituted or unsubstituted cycloalkenylalkyl,substituted or unsubstituted heterocyclealkyl,

a group represented by the formula: —(CR⁷R⁸)n-C(═O)—R⁹, wherein R⁷ andR⁸ are each independently hydrogen, carboxy, substituted orunsubstituted alkyl, substituted or unsubstituted aryl, substituted orunsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl or substituted orunsubstituted heterocycle, n is an integer of 1 to 10, R⁹ is —OR¹⁰ or—NR¹¹R¹², R¹⁰, R¹¹ and R¹² are each independently hydrogen orsubstituted or unsubstituted alkyl or

a group represented by the formula: —C(R⁷R⁸)n-O—R¹³, wherein R⁷, R⁸ andn are as defined in the above, R¹³ is hydrogen or substituted orunsubstituted alkyl,

R³ and R^(4a) taken together with the adjacent nitrogen atom to whichthey are attached may form a substituted or unsubstituted ring,

R⁵ is hydrogen, substituted or unsubstituted alkyl, substituted orunsubstituted alkenyl, substituted or unsubstituted alkynyl, substitutedor unsubstituted aryl, substituted or unsubstituted heteroaryl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedcycloalkenyl, substituted or unsubstituted heterocycle, substituted orunsubstituted alkyloxy, substituted or unsubstituted cycloalkyloxy,substituted or unsubstituted aryloxy, substituted or unsubstitutedheteroaryloxy, substituted or unsubstituted heterocycleoxy, substitutedor unsubstituted alkylthio, substituted or unsubstituted cycloalkylthio,substituted or unsubstituted cycloalkenylthio, substituted orunsubstituted arylthio, substituted or unsubstituted heteroarylthio,substituted or unsubstituted heterocyclethio, substituted orunsubstituted alkylsulfonyl, substituted or unsubstitutedcycloalkylsulfonyl, substituted or unsubstituted cycloalkenylsulfonyl,substituted or unsubstituted arylsulfonyl, substituted or unsubstitutedheteroarylsulfonyl, substituted or unsubstituted heterocyclesulfonyl,substituted or unsubstituted acyl or substituted or unsubstituted amino,

R^(X) is halogen, hydroxy, cyano, nitro, carboxy, substituted orunsubstituted alkyl, substituted or unsubstituted alkenyl, substitutedor unsubstituted aryl, substituted or unsubstituted heteroaryl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedcycloalkenyl, substituted or unsubstituted heterocycle, substituted orunsubstituted alkyloxy, substituted or unsubstituted amino orsubstituted or unsubstituted carbamoyl,

m is an integer of 0 to 3,

with the proviso that compounds, wherein Z¹ is —O—, Ring B is benzene,R⁵ is methyl, m is 0 and R³ and R^(4a) taken together with the adjacentnitrogen atom to which they are attached may form a substituted orunsubstituted ring and the compounds shown as follows are excluded:

(A7)

The compound according to the above (A6), its pharmaceuticallyacceptable salt, or a solvate thereof, wherein Z¹ is —S—,

(A8)

The compound according to the above (A6) or (A7), its pharmaceuticallyacceptable salt, or a solvate thereof, wherein Ring B is aromaticcarbocycle,

(A9)

The compound according to any one of the above (A6) to (A8), itspharmaceutically acceptable salt, or a solvate thereof, wherein Ring Bis benzene,

(A10)

The compound according to the above (A6) or (A7), its pharmaceuticallyacceptable salt, or a solvate thereof, wherein Ring B is monocyclicaromatic hetero ring,

(A11)

The compound according to any one of the above (A6) to (A10), itspharmaceutically acceptable salt, or a solvate thereof, wherein R^(4a)is substituted or unsubstituted arylalkyl or substituted orunsubstituted heteroarylalkyl,

(A12)

The compound according to any one of the above (A6) to (A11), itspharmaceutically acceptable salt, or a solvate thereof, wherein R^(4a)is substituted or unsubstituted arylalkyl,

(A13)

The compound according to any one of the above (A6) to (A11), itspharmaceutically acceptable salt, or a solvate thereof, wherein R^(4a)is

wherein R^(a) is halogen, hydroxy, carboxy, nitro, cyano, azide,substituted or unsubstituted alkyl, substituted or unsubstitutedalkenyl, substituted or unsubstituted alkynyl, substituted orunsubstituted aryl, substituted or unsubstituted cycloalkyl, substitutedor unsubstituted cycloalkenyl, substituted or unsubstituted heteroaryl,substituted or unsubstituted heterocycle, substituted or unsubstitutedalkyloxy, substituted or unsubstituted aryloxy, substituted orunsubstituted silyloxy, substituted or unsubstituted amino, substitutedor unsubstituted carbamoyl, substituted or unsubstituted carbamoyloxy,substituted or unsubstituted acyl, substituted or unsubstitutedalkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted orunsubstituted sulfamoyl or substituted or unsubstitutedalkyloxycarbonyl, R¹⁴ and R¹⁵ are each independently hydrogen, halogen,hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl,substituted or unsubstituted alkenyl or substituted or unsubstitutedalkynyl, b is an integer of 0 to 3,

(A14)

The compound according to the above (A13), its pharmaceuticallyacceptable salt, or a solvate thereof, wherein R^(4a) is

wherein R^(a), R¹⁴ and R¹⁵ are as defined in the above (A13), c is aninteger of 0 to 2,

(A15)

The compound according to any one of the above (A6) to (A14), itspharmaceutically acceptable salt, or a solvate thereof, wherein R¹ andR² are each independently hydrogen, hydroxy or substituted orunsubstituted alkyl,

(A16)

The compound according to any one of the above (A6) to (A15), itspharmaceutically acceptable salt, or a solvate thereof, wherein R³ ishydrogen,

(A17)

The compound according to any one of the above (A6) to (A16), itspharmaceutically acceptable salt, or a solvate thereof, wherein R⁵ ishydrogen, substituted or unsubstituted alkyl, substituted orunsubstituted alkenyl, substituted or unsubstituted alkynyl, substitutedor unsubstituted aryl, substituted or unsubstituted heteroaryl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkyloxy, substituted orunsubstituted aryloxy, substituted or unsubstituted arylsulfonyl orsubstituted or unsubstituted acyl,

(A18)

A pharmaceutical composition comprising the compound according to anyone of the above (A6) to (A17), its pharmaceutically acceptable salt, ora solvate thereof,

(A19)

A pharmaceutical composition comprising the compound according to anyone of the above (A6) to (A17), its pharmaceutically acceptable salt, ora solvate thereof, which has an inhibitory activity on endotheliallipase,

(A20)

The pharmaceutical composition according to the above (A18) for treatingand/or preventing lipid metabolism abnormality,

(A21)

The pharmaceutical composition according to the above (A18) for treatingand/or preventing hyperlipidemia,

(A22)

The pharmaceutical composition according to the above (A18) for treatingand/or preventing arteriosclerosis,

(A23)

A method for preventing or treating lipid metabolism abnormality,comprising administering the compound according to any one of the above(A6) to (A17), its pharmaceutically acceptable salt, or a solvatethereof,

(A24)

A method for preventing or treating hyperlipidemia, comprisingadministering the compound according to any one of the above (A6) to(A17), its pharmaceutically acceptable salt, or a solvate thereof,

(A25)

A method for preventing or treating arteriosclerosis, comprisingadministering the compound according to any one of the above (A6) to(A17), its pharmaceutically acceptable salt, or a solvate thereof,

(A26)

A use of the compound according to any one of the above (A6) to (A17),its pharmaceutically acceptable salt, or a solvate thereof formanufacturing a medicament of treatment and/or prevention of lipidmetabolism abnormality,

(A27)

A use of the compound according to any one of the above (A6) to (A17),its pharmaceutically acceptable salt, or a solvate thereof formanufacturing a medicament of treatment and/or prevention ofhyperlipidemia,

(A28)

A use of the compound according to any one of the above (A6) to (A17),its pharmaceutically acceptable salt, or a solvate thereof formanufacturing a medicament of treatment and/or prevention ofarteriosclerosis,

(A29)

The compound according to any one of the above (A6) to (A17), itspharmaceutically acceptable salt, or a solvate thereof for the treatmentand/or prevention of lipid metabolism abnormality,

(A30)

The compound according to any one of the above (A6) to (A17), itspharmaceutically acceptable salt, or a solvate thereof for the treatmentand/or prevention of hyperlipidemia,

(A31)

The compound according to any one of the above (A6) to (A17), itspharmaceutically acceptable salt, or a solvate thereof for the treatmentand/or prevention of arteriosclerosis.

Effect of the Invention

Since the present compound has inhibitory activity on endotheliallipase, pharmaceutical compositions comprising the present compound arevery useful as medicaments, especially, as medicaments for treatmentand/or prevention of lipid metabolism abnormality, hyperlipidemia,arteriosclerosis, atherosclerosis, hypercholesterolemia,hypertriglyceridemia, diabetes, obesity and/or syndrome X.

Moreover, the present compound selectively inhibits endothelial lipase,and has high selectivity to Hepatic Lipase (HL) and Lipoprotein Lipase(LPL). The present compound is a compound having other utility as amedicament. Here, the utility as a medicament includes high metabolicstability, a weak drug-metabolizing enzyme induction, a weak inhibitionof drug metabolizing enzyme that metabolizes other drug, a high oralabsorption, a low clearance, a long half-life period enough to exhibitdrug efficacy and so on.

BEST MODE FOR CARRYING OUT THE INVENTION

In the following, meanings of terms used in the present specificationwill be explained. Each term has the same meaning when used alone or incombination with other term in this description.

“Halogen” includes fluorine, chlorine, bromine or iodine.

“Alkyl” means a C1 to C10 straight or branched alkyl group, and exampleincludes methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl,isohexyl, n-heptyl, n-octyl, n-nonyl, n-decyl or the like. Preferable isC1 to C6 or C1 to C4 alkyl, and example includes methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl,isopentyl, neopentyl, n-hexyl or isohexyl.

“Alkenyl” means C2 to C8 straight or branched alkenyl having one or moredouble bond(s) in the above “alkyl”, and example includes vinyl,1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1,3-butadienyl,3-methyl-2-butenyl or the like.

“Alkynyl” means C2 to C8 straight or branched alkynyl having one or moretriple bond(s) in the above “alkyl”, and example includes ethynyl,propinyl, butynyl or the like. Furthermore, “Alkynyl” may have a doublebond.

“Cycloalkyl” means a C3 to C15 cyclic saturated hydrocarbon group, andexample includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl, cyclooctyl, bridged cyclic hydrocarbon group, Spirohydrocarbon group or the like. Preferable is cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl or bridged cyclic hydrocarbon group.

“Bridged cyclic hydrocarbon group” includes a group which is derived byexcluding one hydrogen from a C5 to C8 aliphatic cycle which consists oftwo or more rings that share two or more atoms. Example includesbicyclo[2.1.0]pentyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl,bicyclo[3.2.1]octyl, tricyclo[2.2.1.0]heptyl or the like.

“Spiro hydrocarbon group” includes a group which is derived by excludingone hydrogen from a cycle which consists of two hydrocarbon rings thatshare one carbon atom. Example includes spiro[3.4]octyl or the like.

“Cycloalkenyl” means C3 to C10 cyclic unsaturated aliphatic hydrocarbongroup, and example includes cyclopropenyl (e.g.: 1-cyclopropenyl),cyclobutenyl (e.g.: 1-cyclobutenyl), cyclopentenyl (e.g.:1-cyclopenten-1-yl, 2-cyclopenten-1-yl or 3-cyclopenten-1-yl),cyclohexenyl (e.g.: 1-cyclohexen-1-yl, 2-cyclohexen-1-yl or3-cyclohexen-1-yl), cycloheptenyl (e.g.: 1-cycloheptenyl), cyclooctenyl(e.g.: 1-cyclooctenyl) or the like. Preferable is cyclopropenyl,cyclobutenyl, cyclopentenyl or cyclohexenyl. Cycloalkenyl also includesbridged cyclic hydrocarbon group and spiro hydrocarbon group which havean unsaturated bond in the ring.

“Aryl” means a monocyclic aromatic hydrocarbon group (e.g.: phenyl) anda polycyclic aromatic hydrocarbon group (e.g.: 1-naphthyl, 2-naphthyl,1-anthryl, 2-anthryl, 9-anthryl, 1-phenanthryl, 2-phenanthryl,3-phenanthryl, 4-phenanthryl or 9-phenanthryl). Preferable is phenyl ornaphthyl (1-naphthyl or 2-naphthyl).

“Heteroaryl” means a monocyclic aromatic heterocyclic group or a fusedaromatic heterocyclic group. The monocyclic aromatic heterocyclic groupmeans a group derived from a 5- to 8-membered aromatic ring which maycontain 1 to 4 oxygen, sulfur and/or nitrogen atom(s) in the ring, andmay have a bond at a substitutable arbitrary position.

The fused aromatic heterocyclic group means a group in which a 5- to8-membered aromatic ring optionally containing 1 to 4 oxygen, sulfurand/or nitrogen atom(s) in the ring is fused with 1 to 4 of 5- to8-membered aromatic carbocycle(s) or other 5- to 8-membered aromaticheterocycle(s), and which may have a bond at a substitutable arbitraryposition.

Example of the “heteroaryl” includes furyl (e.g.: 2-furyl or 3-furyl),thienyl (e.g.: 2-thienyl or 3-thienyl), pyrrolyl (e.g.: 1-pyrrolyl,2-pyrrolyl or 3-pyrrolyl), imidazolyl (e.g.: 1-imidazolyl, 2-imidazolylor 4-imidazolyl), pyrazolyl (e.g.: 1-pyrazolyl, 3-pyrazolyl or4-pyrazolyl), triazolyl (e.g.: 1,2,4-triazole-1-yl, 1,2,4-triazole-3-ylor 1,2,4-triazole-4-yl), tetrazolyl (e.g.: 1-tetrazolyl, 2-tetrazolyl or5-tetrazolyl), oxazolyl (e.g.: 2-oxazolyl, 4-oxazolyl or 5-oxazolyl),isoxazolyl (e.g.: 3-isoxazolyl, 4-isoxazolyl or 5-isoxazolyl), thiazolyl(e.g.: 2-thiazolyl, 4-thiazolyl or 5-thiazolyl), thiadiazolyl,isothiazolyl (e.g.: 3-isothiazolyl, 4-isothiazolyl or 5-isothiazolyl),pyridyl (e.g.: 2-pyridyl, 3-pyridyl or 4-pyridyl), pyridazinyl (e.g.:3-pyridazinyl or 4-pyridazinyl), pyrimidinyl (e.g.: 2-pyrimidinyl,4-pyrimidinyl or 5-pyrimidinyl), furazanyl (e.g.: 3-furazanyl),pyrazinyl (e.g.: 2-pyrazinyl), oxadiazolyl (e.g.:1,3,4-oxadiazole-2-yl), benzofuryl (e.g.: 2-benzo[b]furyl,3-benzo[b]furyl, 4-benzo[b]furyl, 5-benzo[b]furyl, 6-benzo[b]furyl or7-benzo[b]furyl), benzothienyl (e.g.: 2-benzo[b]thienyl,3-benzo[b]thienyl, 4-benzo[b]thienyl, 5-benzo[b]thienyl,6-benzo[b]thienyl or 7-benzo[b]thienyl), benzimidazolyl (e.g.:1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl or5-benzimidazolyl), dibenzofuryl, benzoxazolyl, benzothiazolyl,quinoxalinyl (e.g.: 2-quinoxalinyl, 5-quinoxalinyl or 6-quinoxalinyl),cinnolinyl (e.g.: 3-cinnolinyl, 4-cinnolinyl, 5-cinnolinyl,6-cinnolinyl, 7-cinnolinyl or 8-quinazolinyl (e.g.: 2-quinazolinyl,4-quinazolinyl, 5-quinazolinyl, 6-quinazolinyl, 7-quinazolinyl or8-quinazolinyl), quinolyl (e.g.: 2-quinolyl, 3-quinolyl, 4-quinolyl,5-quinolyl, 6-quinolyl, 7-quinolyl or 8-quinolyl), phthalazinyl (e.g.:1-phthalazinyl, 5-phthalazinyl or 6-phthalazinyl), isoquinolyl (e.g.:1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl,6-isoquinolyl, 7-isoquinolyl or 8-isoquinolyl), puryl, pteridinyl (e.g.:2-pteridinyl, 4-pteridinyl, 6-pteridinyl or 7-pteridinyl), carbazolyl,phenanthridinyl, acridinyl (e.g.: 1-acridinyl, 2-acridinyl, 3-acridinyl,4-acridinyl or 9-acridinyl), indolyl (e.g.: 1-indolyl, 2-indolyl,3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl or 7-indolyl), isoindolyl,phenadinyl (e.g.: 1-phenadinyl or 2-phenadinyl), phenothiadinyl (e.g.:1-phenothiadinyl, 2-phenothiadinyl, 3-phenothiadinyl or4-phenothiadinyl) or the like.

“Heterocycle” means a nonaromatic heterocyclic group which contains atleast one nitrogen, oxygen or sulfur atom(s) in the ring, and may have abond at a substitutable arbitrary position. Moreover, the nonaromaticheterocyclic group can be bridged with a C1 to C4 alkyl chain, or can befused with cycloalkane (5- to 6-membered ring is preferable) or benzenering. “Nonaromatic heterocyclic group” can be saturated or unsaturatedas long as it is non-aromatic. Preferable is a 5- to 8-membered ring.Example includes 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl,1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 1-imidazolinyl,2-imidazolinyl, 4-imidazolinyl, 1-imidazolidinyl, 2-imidazolidinyl,4-imidazolidinyl, 1-pyrazolinyl, 3-pyrazolinyl, 4-pyrazolinyl,1-pyrazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, piperidino,2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-piperadinyl,2-piperadinyl, 2-morpholinyl, 3-morpholinyl, morpholino,tetrahydropyranyl, the following groups or the like.

“Acyl” means formyl, substituted or unsubstituted alkylcarbonyl,substituted or unsubstituted alkenylcarbonyl, substituted orunsubstituted cycloalkylcarbonyl, substituted or unsubstitutedcycloalkenylcarbonyl, substituted or unsubstituted arylcarbonyl,substituted or unsubstituted heteroarylcarbonyl or substituted orunsubstituted heterocyclecarbonyl.

The alkyl part of “substituted or unsubstituted alkyloxy”, “substitutedor unsubstituted alkylthio”, “substituted or unsubstitutedalkylsulfonyl”, “substituted or unsubstituted arylalkyl”, “substitutedor unsubstituted heteroarylalkyl”, “substituted or unsubstitutedcycloalkylalkyl”, “substituted or unsubstituted cycloalkenylalkyl”,“substituted or unsubstituted heterocyclealkyl” and “substituted orunsubstituted alkyloxycarbonyl” means the above “alkyl”.

The cycloalkyl part of “substituted or unsubstituted cycloalkyloxy”,“substituted or unsubstituted cycloalkylthio”, “substituted orunsubstituted cycloalkylsulfonyl” and “substituted or unsubstitutedcycloalkylalkyl” means the above “cycloalkyl”.

The cycloalkenyl part of “substituted or unsubstitutedcycloalkenylthio”, “substituted or unsubstituted cycloalkenylsulfonyl”,“substituted or unsubstituted cycloalkenyloxy” and “substituted orunsubstituted cycloalkenylalkyl” means the above “cycloalkenyl”.

The aryl part of “substituted or unsubstituted aryloxy”, “substituted orunsubstituted arylthio”, “substituted or unsubstituted arylsulfonyl” and“substituted or unsubstituted arylalkyl” means the above “aryl”.

The heteroaryl part of “substituted or unsubstituted heteroaryloxy”,“substituted or unsubstituted heteroarylthio”, “substituted orunsubstituted heteroarylsulfonyl” and “substituted or unsubstitutedheteroarylalkyl” means the above “heteroaryl”.

The heterocycle part of “substituted or unsubstituted heterocycleoxy”,“substituted or unsubstituted heterocyclethio”, “substituted orunsubstituted heterocyclesulfonyl” and “substituted or unsubstitutedheterocyclealkyl” means the above “heterocycle.”

“Hetero ring” means a ring which contains one or more heteroatom(s)selected from the group consisting of N, O and S in the ring. The ringincludes a monocycle or a fused ring (bicyclic ring is preferable), andincludes an aromatic hetero ring or a nonaromatic hetero ring. As the“hetero ring”, for example, the following examples are included:

When the above “hetero ring” has a substituent, a substitutablearbitrary position may be substituted and hydrogen of —NH— may bereplaced.

“Nitrogen-containing hetero ring” means a ring which contains at leastone N in the ring, and moreover may contain O, S or N(R⁶). The ringincludes a monocycle or a fused ring, and may include an aromatic heteroring or a nonaromatic hetero ring. For example, the following examplesare included:

When the above “nitrogen-containing hetero ring” has a substituent, asubstitutable arbitrary position may be substituted and hydrogen of —NH—may be replaced.

“substituted or unsubstituted alkyl”, “substituted or unsubstitutedalkenyl”, “substituted or unsubstituted alkynyl”, “substituted orunsubstituted aryl”, “substituted or unsubstituted heteroaryl”,“substituted or unsubstituted cycloalkyl”, “substituted or unsubstitutedcycloalkenyl”, “substituted or unsubstituted heterocycle”, “substitutedor unsubstituted alkyloxy”, “substituted or unsubstitutedcycloalkyloxy”, “substituted or unsubstituted aryloxy”, “substituted orunsubstituted heteroaryloxy”, “substituted or unsubstitutedheterocycleoxy”, “substituted or unsubstituted alkylthio”, “substitutedor unsubstituted cycloalkylthio”, “substituted or unsubstitutedcycloalkenylthio”, “substituted or unsubstituted arylthio”, “substitutedor unsubstituted heteroarylthio”, “substituted or unsubstitutedheterocyclethio”, “substituted or unsubstituted alkylsulfonyl”,“substituted or unsubstituted cycloalkylsulfonyl”, “substituted orunsubstituted cycloalkenylsulfonyl”, “substituted or unsubstitutedarylsulfonyl”, “substituted or unsubstituted heteroarylsulfonyl”,“substituted or unsubstituted heterocyclesulfonyl”, “substituted orunsubstituted acyl”, “substituted or unsubstituted arylalkyl”,“substituted or unsubstituted heteroarylalkyl”, “substituted orunsubstituted cycloalkylalkyl”, “substituted or unsubstitutedcycloalkenylalkyl”, “substituted or unsubstituted heterocyclealkyl”,“substituted or unsubstituted carbamoyl”, “substituted or unsubstitutedsilyloxy”, “substituted or unsubstituted carbamoyloxy”, “substituted orunsubstituted sulfamoyl”, “substituted or unsubstitutedalkyloxycarbonyl”, “a ring formed by taking together R³ and R⁴ with theadjacent nitrogen atom to which they are attached” or “a ring formed bytaking together R³ and R^(4a) with the adjacent nitrogen atom to whichthey are attached” may be substituted with 1 to 4 substituent(s)selected from a group consisting of, for example,

halogen, hydroxy, carboxy, nitro, cyano,substituted or unsubstituted alkyl (example of a substituent ofsubstituted alkyl includes halogen, hydroxy, carboxy, cyano, amino,alkyl, aryl, cycloalkyl, heteroaryl, heterocycle, alkyloxycarbonyl,alkyloxycarbonylamino or carbamoyl. e.g.: methyl, ethyl, isopropyl,tert-butyl, CF₃, CH₂OH, CH₂COOCH₃, CH₂NH₂, benzyl, cyclopentylmethyl,tert-butoxycarbonylaminomethyl or methoxycarbonylmethyl), substituted orunsubstituted alkenyl (example of a substituent of substituted alkenylincludes halogen, carboxy, alkyl, aryl, cycloalkyl, heteroaryl orheterocycle. e.g.: vinyl),substituted or unsubstituted alkynyl (example of a substituent ofsubstituted alkynyl includes halogen, alkyl, aryl, cycloalkyl,heteroaryl or heterocycle. e.g.: ethynyl), substituted or unsubstitutedaryl (example of a substituent of substituted aryl includes halogen,alkyl, aryl, cycloalkyl, heteroaryl or heterocycle. e.g.: phenyl ornaphthyl),substituted or unsubstituted cycloalkyl (example of a substituent ofsubstituted cycloalkyl includes halogen, alkyl, aryl, cycloalkyl,heteroaryl or heterocycle. e.g.: cyclopropyl),substituted or unsubstituted cycloalkenyl (example of a substituent ofsubstituted cycloalkenyl includes halogen, alkyl, aryl, cycloalkyl,heteroaryl or heterocycle. e.g.: cyclopropenyl),substituted or unsubstituted heteroaryl (example of a substituent ofsubstituted heteroaryl includes halogen, alkyl, aryl, cycloalkyl,heteroaryl or heterocycle. e.g.: tetrazolyl, indolyl or pyrazolyl),substituted or unsubstituted heterocycle (example of a substituent ofsubstituted heterocycle includes halogen, alkyl, aryl, cycloalkyl,heteroaryl or heterocycle. e.g.: pyrrolidinyl, morpholinyl, piperazinylor piperidyl),substituted or unsubstituted alkyloxy (example of a substituent ofsubstituted alkyloxy includes halogen, carboxy, cyano, alkyl, aryl,cycloalkyl, heteroaryl or heterocycle. e.g.: methoxy, ethoxy, propoxy,butoxy or OCF₃),substituted or unsubstituted aryloxy (example of a substituent ofsubstituted aryloxy includes halogen, alkyl, aryl, cycloalkyl,heteroaryl or heterocycle. e.g.: phenyloxy), substituted orunsubstituted silyloxy,substituted or unsubstituted amino (e.g.: alkylamino (e.g.: methylamino,ethylamino or dimethylamino), acylamino (e.g.: acetylamino orbenzoylamino), arylalkylamino (e.g.: benzylamino or tritylamino),hydroxyamino, alkylaminoalkyl (e.g.: diethylaminomethyl),alkyloxycarbonylamino, alkylsulfonylamino, carbamoylamino,heterocyclecarbonylamino, arylsulfonylamino, heteroarylsulfonylamino),substituted or unsubstituted carbamoyl (example of a substituent ofsubstituted carbamoyl includes hydroxy, cyano, substituted orunsubstituted alkyl, alkyloxy or alkylsulfonyl. e.g.: alkylcarbamoyl(e.g.: methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl,phenylethylcarbamoyl, dimethylaminoethylcarbamoyl, isopropylcarbamoyl orhydroxyethylcarbamoyl), alkylsulfonylcarbamoyl, heteroarylalkylcarbamoylor substituted or unsubstituted alkyloxycarbamoyl), substituted orunsubstituted carbamoyloxy (example of a substituent of substitutedcarbamoyloxy includes halogen, alkyl, aryl, cycloalkyl, heteroaryl orheterocycle), substituted or unsubstituted acyl (example of asubstituent of substituted acyl includes halogen, alkyl, aryl,cycloalkyl, heteroaryl or heterocycle. e.g.: alkylcarbonyl,arylcarbonyl, heteroarylcarbonyl, heterocyclecarbonyl, formyl oracetyl),substituted or unsubstituted alkylsulfonyl (example of a substituent ofsubstituted alkylsulfonyl includes halogen, alkyl, aryl, cycloalkyl,heteroaryl or heterocycle. e.g.: methanesulfonyl or ethanesulfonyl),substituted or unsubstituted arylsulfonyl,substituted or unsubstituted heteroarylsulfonyl (example of asubstituent of substituted heteroarylsulfonyl includes halogen, alkyl,aryl, cycloalkyl, heteroaryl or heterocycle),substituted or unsubstituted sulfamoyl,substituted or unsubstituted alkyloxycarbonyl (example of a substituentof substituted alkyloxycarbonyl includes halogen, alkyl, aryl,cycloalkyl, heteroaryl or heterocycle. e.g.: methoxycarbonyl,ethoxycarbonyl or tort-butoxycarbonyl), aryloxycarbonyl,heteroaryloxycarbonyl, heterocycleoxycarbonyl, cycloalkylsulfonyl,heteroarylsulfonyl, heterocyclesulfonyl, alkylsulfinyl,cycloalkylsulfinyl, arylsulfinyl, heteroarylsulfinyl,heterocyclesulfinyl,nitroso,alkenyloxy (e.g.: vinyloxy or allyloxy),arylalkyloxy (e.g.: benzyloxy),azide,isocyano, isocyanato, thiocyanato, isothiocyanato, mercapto,alkylthio (e.g.: methylthio),formyloxy, haloformyl, oxalo, thioformyl, thiocarboxy, dithiocarboxy,thiocarbamoyl, sulfino, sulfo, sulfoamino, hydrazino, ureide, amidino,guanidino, phthalimide, oxo and the like.

Example of a substituent of “substituted or unsubstituted amino”,“substituted or unsubstituted carbamoyl”, “substituted or unsubstitutedcarbamoyloxy” or “substituted or unsubstituted sulfamoyl” includesalkyl, alkenyl, substituted or unsubstituted aryl (example of asubstituent of substituted aryl includes carboxy, alkyloxy orsulfamoyl), heteroaryl, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl,heterocyclecarbonyl, alkyloxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, heterocycleoxycarbonyl, sulfamoyl, alkylsulfonyl,carbamoyl, cycloalkylsulfonyl, arylsulfonyl, heteroarylsulfonyl,heterocyclesulfonyl, acyl, hydroxy, alkylsulfinyl, cycloalkylsulfinyl,arylsulfinyl, heteroarylsulfinyl, heterocyclesulfinyl, amino or thelike.

The alkyl part of “alkyloxycarbonyl”, “alkyloxycarbonylamino”,“alkylamino”, “arylalkylamino”, “alkylaminoalkyl”,“alkyloxycarbonylamino”, “alkylsulfonylamino”, “alkylcarbamoyl”,“alkylsulfonylcarbamoyl”, “substituted or unsubstitutedalkyloxycarbamoyl”, “alkylcarbonyl”, “alkylsulfinyl”, “arylalkyloxy”,“alkylthio” and “alkylsulfonyl” means the above “alkyl”.

The alkenyl part of “alkenyloxy” means the above “alkenyl”.

The aryl part of “arylalkylamino”, “arylsulfonylamino”, “arylcarbonyl”,“aryloxycarbonyl”, “arylsulfinyl”, “arylalkyloxy” and “arylsulfonyl”means the above “aryl”.

The heteroaryl part of “heteroarylcarbonyl”, “heteroaryloxycarbonyl”,“heteroarylsulfonyl” and “heteroarylsulfinyl” means the above“heteroaryl”.

The heterocycle part of “heterocyclecarbonyl”,“heterocyclecarbonylamino”, “heterocycleoxycarbonyl”,“heterocyclesulfonyl” and “heterocyclesulfinyl” means the above“heterocycle.”

The cycloalkyl part of “cycloalkylsulfonyl” and “cycloalkylsulfinyl”means the above “cycloalkyl”.

Among the present compound, the following embodiments are preferable.

Ring A in the formula (I) is nitrogen-containing hetero ring in whichone atom neighboring to the carbon atom binding to a group representedby the formula: —C(R¹R²)—C(═O)—NR³R⁴ is nitrogen atom and the other atomis heteroatom. The broken line in the formula (I) means the presence orabsence of a bond.

Ring A is not only a monocycle but also a fused ring (2 to 3 fusedring), and especially a monocycle or a bicycle is preferable. Ring A mayinclude a heteroatom other than the nitrogen atom shown in the aboveformula (I) and the constituent atom of the Ring A includes carbon atom,oxygen atom, nitrogen atom or sulfur atom. The bond constructing theRing A includes a single bond or a double bond.

Ring A may be substituted with a substituent other than a grouprepresented by the formula: —C(R¹R²)—C(═O)—NR³R⁴ and a group representedby the formula: —R⁵.

For example, as the group represented by the formula:

the following rings are included:

wherein R⁵ and R⁶ have the same meaning as the above. In the aboveformula, a substitutable arbitrary position in Ring A may be substitutedwith R⁵. A constituent atom of the Ring A other than a position which issubstituted with R⁵ and R⁶ may be substituted with a substituent otherthan R⁵ and R⁶.

Preferably, the following rings are included:

More preferably, the following rings are included:

Particular preferably, the following rings are included:

In the above Ring A, a substitutable arbitrary position may besubstituted with a substituent other than R⁵ and R⁶.

As a substituent other than a group represented by the formula:—C(R¹R²)—C(═O)—NR³R⁴ and a group represented by the formula: —R⁵,example includes halogen, hydroxy, cyano, nitro, carboxy, substituted orunsubstituted alkyl, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkyloxy, substituted orunsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted cycloalkyloxy, substituted or unsubstitutedcycloalkenyloxy, substituted or unsubstituted heterocycleoxy,substituted or unsubstituted alkylthio, substituted or unsubstitutedarylthio, substituted or unsubstituted heteroarylthio, substituted orunsubstituted cycloalkylthio, substituted or unsubstitutedcycloalkenylthio, substituted or unsubstituted heterocyclethio,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedarylsulfonyl, substituted or unsubstituted heteroarylsulfonyl,substituted or unsubstituted cycloalkylsulfonyl, substituted orunsubstituted cycloalkenylsulfonyl, substituted or unsubstitutedheterocyclesulfonyl, substituted or unsubstituted acyl, substituted orunsubstituted carbamoyl, substituted or unsubstituted amino or the like.Ring A may be substituted with 1 to 3 of the substituent(s).

Z is —NR⁶—, ═N—, —O—, or —S—. Preferable is —O— or —S— and morepreferable is —S—.

R⁶ of —NR⁶— in Z is hydrogen, substituted or unsubstituted alkyl,substituted or unsubstituted alkenyl, substituted or unsubstitutedalkynyl, substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl or substituted or unsubstituted heterocycle.Preferable is hydrogen or substituted or unsubstituted alkyl.

R¹ and R² are each independently hydrogen, halogen, cyano, nitro,carboxy or substituted or unsubstituted alkyl. Preferable is hydrogen orsubstituted or unsubstituted alkyl. More preferable is hydrogen.

R³ is hydrogen or substituted or unsubstituted alkyl. Preferable ishydrogen.

R⁴ is hydrogen, substituted or unsubstituted alkyl, substituted orunsubstituted alkenyl, substituted or unsubstituted alkynyl, substitutedor unsubstituted aryl, substituted or unsubstituted heteroaryl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedcycloalkenyl, substituted or unsubstituted heterocycle or substituted orunsubstituted amino.

Preferable is substituted or unsubstituted alkyl, substituted orunsubstituted aryl, substituted or unsubstituted heteroaryl, substitutedor unsubstituted cycloalkyl, substituted or unsubstituted heterocycle orsubstituted or unsubstituted amino.

More preferable is substituted or unsubstituted alkyl.

R⁵ is hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted orunsubstituted alkyl, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkyloxy, substituted orunsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted cycloalkyloxy, substituted or unsubstitutedcycloalkenyloxy, substituted or unsubstituted heterocycleoxy,substituted or unsubstituted alkylthio, substituted or unsubstitutedarylthio, substituted or unsubstituted heteroarylthio, substituted orunsubstituted cycloalkylthio, substituted or unsubstitutedcycloalkenylthio, substituted or unsubstituted heterocyclethio,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedarylsulfonyl, substituted or unsubstituted heteroarylsulfonyl,substituted or unsubstituted cycloalkylsulfonyl, substituted orunsubstituted cycloalkenylsulfonyl, substituted or unsubstitutedheterocyclesulfonyl, substituted or unsubstituted acyl, substituted orunsubstituted carbamoyl or substituted or unsubstituted amino.

Preferable is substituted or unsubstituted aryl, substituted orunsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedheterocycle, substituted or unsubstituted aryloxy, substituted orunsubstituted heteroaryloxy, substituted or unsubstituted cycloalkyloxy,substituted or unsubstituted cycloalkenyloxy, substituted orunsubstituted heterocycleoxy, substituted or unsubstituted arylthio,substituted or unsubstituted heteroarylthio, substituted orunsubstituted cycloalkylthio, substituted or unsubstitutedcycloalkenylthio, substituted or unsubstituted heterocyclethio,substituted or unsubstituted arylsulfonyl, substituted or unsubstitutedheteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl,substituted or unsubstituted cycloalkenylsulfonyl, substituted orunsubstituted heterocyclesulfonyl or substituted or unsubstituted amino.

More preferable is substituted or unsubstituted aryl, substituted orunsubstituted heteroaryl, substituted or unsubstituted aryloxy,substituted or unsubstituted heteroaryloxy, substituted or unsubstitutedarylthio, substituted or unsubstituted heteroarylthio, substituted orunsubstituted arylsulfonyl, substituted or unsubstitutedheteroarylsulfonyl or substituted or unsubstituted amino.

Z¹ is —O— or —S—. Preferable is —S—.

Ring B in the formula (II) is aromatic carbocycle, aromatic hetero ring,nonaromatic carbocycle or nonaromatic hetero ring which is fused withthe adjacent 5 membered ring. A substitutable arbitrary position in RingB is substituted with R⁵ (including hydrogen), a substitutable arbitraryposition other than a position which is substituted with R⁵ may besubstituted with 0 to 3 of R^(X).

“Aromatic carbocycle” means a monocyclic aromatic carbocycle (e.g.:benzene ring) or a fused aromatic carbocycle. Herein, as the “fusedaromatic carbocycle”, example includes C10 to C14 fused aromaticcarbocycle or the like. Example includes naphthalene, phenanthrene,anthracene or the like.

“Aromatic hetero ring” means a aromatic ring which contains one or moreheteroatom(s) selected from the group consisting of nitrogen atom,sulfur atom and oxygen atom other than the carbon atom in the ring. Thering includes a monocycle or a fused ring.

“Nonaromatic carbocycle” means a 5 to 10 membered nonaromatic carbocyclewhich may have a saturated or an unsaturated bond partially and may befused with aryl or heteroaryl.

“Nonaromatic hetero ring” means a nonaromatic ring which contains one ormore heteroatom(s) selected from the group consisting of nitrogen atom,sulfur atom and oxygen atom other than the carbon atom in the ring. Thering means a 5 to 10 membered ring which may have a saturated or anunsaturated bond partially and may be fused with aryl or aromatic heteroring.

As the Ring B, for example, the following rings are included. In thefollowing rings, a substitutable arbitrary position other than aposition which is substituted with R⁵ (including hydrogen) may besubstituted with 0 to 3 of R^(X).

Herein, R⁵ has the same meaning as the above.

Preferably, the following rings are included:

More preferably, the following rings are included:

Particular preferably, the following rings are included:

R^(4a) is substituted or unsubstituted arylalkyl, substituted orunsubstituted heteroarylalkyl, substituted or unsubstitutedcycloalkylalkyl, substituted or unsubstituted cycloalkenylalkyl,substituted or unsubstituted heterocyclealkyl,

a group represented by the formula: —(CR⁷R⁸)n-C(═O)—R⁹, wherein R⁷ andR⁸ are each independently hydrogen, halogen, hydroxy, carboxy,substituted or unsubstituted alkyl, substituted or unsubstitutedalkyloxy, substituted or unsubstituted aryl, substituted orunsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl or substituted orunsubstituted heterocycle, n is an integer of 1 to 10, R⁹ is —OR¹⁰ or—NR¹¹R¹², R¹⁰ is hydrogen, substituted or unsubstituted alkyl,substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl or substituted or unsubstituted heterocycle,R¹¹ and R¹² are each independently hydrogen, substituted orunsubstituted alkyl, substituted or unsubstituted alkyloxy, substitutedor unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedaryl, substituted or unsubstituted heteroaryl, substituted orunsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl orsubstituted or unsubstituted heterocycle or

a group represented by the formula: —C(R⁷R⁸)n-O—R¹³, wherein R⁷, R⁸ andn are as defined in the above, R¹³ is hydrogen or substituted orunsubstituted alkyl.

Preferable is substituted or unsubstituted arylalkyl, substituted orunsubstituted heteroarylalkyl or a group represented by the formula:—(CR⁷R⁸)n-C(═O)—R⁹.

Especially as the substituted or unsubstituted arylalkyl or substitutedor unsubstituted heteroarylalkyl in R^(4a), the following groups arepreferably included:

wherein R^(a), R¹⁴, and R¹⁵ are as defined in the above (18).

b is an integer of 0 to 3. Preferable is 1 or 2.

As the substituted or unsubstituted arylalkyl or substituted orunsubstituted heteroarylalkyl in R^(4a), the following groups are morepreferably included:

wherein R^(a), R¹⁴, and R¹⁵ are as defined in the above (18).

c is an integer of 0 to 2.

R^(a) is halogen, hydroxy, carboxy, nitro, cyano, azide, substituted orunsubstituted alkyl, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl,substituted or unsubstituted heteroaryl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkyloxy, substituted orunsubstituted aryloxy, substituted or unsubstituted silyloxy,substituted or unsubstituted amino, substituted or unsubstitutedcarbamoyl, substituted or unsubstituted carbamoyloxy, substituted orunsubstituted acyl, substituted or unsubstituted alkylsulfonyl,substituted or unsubstituted arylsulfonyl, substituted or unsubstitutedheterocyclesulfonyl, substituted or unsubstituted sulfamoyl orsubstituted or unsubstituted alkyloxycarbonyl.

Preferable is carboxy, cyano, substituted or unsubstituted heteroaryl,substituted or unsubstituted amino, substituted or unsubstitutedcarbamoyl, substituted or unsubstituted carbamoyloxy, substituted orunsubstituted alkylsulfonyl or substituted or unsubstituted sulfamoyl.

More preferable is carboxy, substituted or unsubstituted heteroaryl,substituted or unsubstituted carbamoyl, substituted or unsubstitutedcarbamoyloxy, substituted or unsubstituted alkylsulfonyl or substitutedor unsubstituted sulfamoyl.

R⁷ and R⁸ are each independently hydrogen, halogen, hydroxy, carboxy,substituted or unsubstituted alkyl, substituted or unsubstitutedalkyloxy, substituted or unsubstituted aryl, substituted orunsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl or substituted orunsubstituted heterocycle.

Preferable is hydrogen.

n is an integer of 1 to 10. Preferable is an integer of 1 to 3. Morepreferable is 1.

R¹⁰ is hydrogen, substituted or unsubstituted alkyl, substituted orunsubstituted aryl, substituted or unsubstituted heteroaryl, substitutedor unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenylor substituted or unsubstituted heterocycle.

Preferable is hydrogen or substituted or unsubstituted alkyl.

R¹¹ and R¹² are each independently hydrogen, substituted orunsubstituted alkyl, substituted or unsubstituted alkyloxy, substitutedor unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedaryl, substituted or unsubstituted heteroaryl, substituted orunsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl orsubstituted or unsubstituted heterocycle.

R¹¹ is preferably hydrogen.

R¹² is preferably substituted or unsubstituted alkyl, substituted orunsubstituted alkyloxy, substituted or unsubstituted aryloxy,substituted or unsubstituted heteroaryloxy, substituted or unsubstitutedalkylsulfonyl, substituted or unsubstituted aryl, substituted orunsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl or substituted orunsubstituted heterocycle.

“A ring formed by taking together R³ and R⁴ with the adjacent nitrogenatom to which they are attached” and “a ring formed by taking togetherR³ and R^(4a) with the adjacent nitrogen atom to which they areattached” mean 3- to 15-membered nonaromatic hetero ring which maycontain 1 to 4 oxygen, sulfur, and/or nitrogen atom(s) besides the abovenitrogen atom in the ring. Moreover, the nonaromatic hetero ring can bebridged with a C1 to C4 alkyl chain, or can be fused with cycloalkane(5- to 6-membered ring is preferable) or benzene ring. The ring can besaturated or unsaturated partially as long as it is nonaromatic.Preferable is a 5- to 8-membered ring. For example, the following groupsare exemplified.

Herein, R¹⁶ is hydrogen or substituted or unsubstituted alkyl.

Preferably, the following groups are exemplified.

R^(X) is halogen, hydroxy, cyano, nitro, carboxy, substituted orunsubstituted alkyl, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkyloxy, substituted orunsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted cycloalkyloxy, substituted or unsubstitutedcycloalkenyloxy, substituted or unsubstituted heterocycleoxy,substituted or unsubstituted alkylthio, substituted or unsubstitutedarylthio, substituted or unsubstituted heteroarylthio, substituted orunsubstituted cycloalkylthio, substituted or unsubstitutedcycloalkenylthio, substituted or unsubstituted heterocyclethio,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedarylsulfonyl, substituted or unsubstituted heteroarylsulfonyl,substituted or unsubstituted cycloalkylsulfonyl, substituted orunsubstituted cycloalkenylsulfonyl, substituted or unsubstitutedheterocyclesulfonyl, substituted or unsubstituted acyl, substituted orunsubstituted carbamoyl or substituted or unsubstituted amino.

m is an integer of 0 to 3. Preferable is 0 or 1.

X in the formula (III) and (IV) is —CR^(X)═, —CH═ or —N═. Preferable is—CH═.

Y in the formula (III) and (IV) is —CR^(X)═, —CH═ or —N═. Preferable is—CH═.

Ring C in the formula (V) is a monocyclic or bicyclic hetero ring andmay include an aromatic hetero ring or a nonaromatic hetero ring. Asubstitutable arbitrary position in Ring C is substituted with R⁵(including hydrogen) and a substitutable arbitrary position other than aposition which is substituted with R⁵ may be substituted with 0 to 3 ofR^(X).

The constituent atom of the Ring C includes carbon atom, oxygen atom,nitrogen atom or sulfur atom. The bond constructing the Ring C includesa single bond or a double bond.

For example, the following rings are exemplified.

A substitutable arbitrary position in the above Ring C may besubstituted with a group represented by the formula:—CH₂—C(═O)—NHR^(4b), a group represented by the formula: —R⁵ and a grouprepresented by the formula: —R^(X).

Hydrogen of —NH— in the above ring may be replaced by a grouprepresented by the formula: —CH₂—C(═O)—NHR^(4b), a group represented bythe formula: —R⁵ or a group represented by the formula: —R^(X).

R^(4b) in the formula (V) is substituted arylalkyl, wherein asubstituent on a ring of the substituted arylalkyl is carboxy,substituted or unsubstituted carbamoyl, substituted or unsubstitutedalkylsulfonyl or substituted or unsubstituted sulfamoyl, substitutedheteroarylalkyl, wherein a substituent on a ring of the substitutedheteroarylalkyl is carboxy, substituted or unsubstituted carbamoyl,substituted or unsubstituted alkylsulfonyl or substituted orunsubstituted sulfamoyl, substituted cycloalkylalkyl, wherein asubstituent on a ring of the substituted cycloalkylalkyl is carboxy,substituted or unsubstituted carbamoyl, substituted or unsubstitutedalkylsulfonyl or substituted or unsubstituted sulfamoyl, substitutedcycloalkenylalkyl, wherein a substituent on a ring of the substitutedcycloalkenylalkyl is carboxy, substituted or unsubstituted carbamoyl,substituted or unsubstituted alkylsulfonyl or substituted orunsubstituted sulfamoyl, substituted heterocyclealkyl, wherein asubstituent on a ring of the substituted heterocyclealkyl is carboxy,substituted or unsubstituted carbamoyl, substituted or unsubstitutedalkylsulfonyl or substituted or unsubstituted sulfamoyl or

a group represented by the formula: —(CR⁷R⁸)n-C(═O)—R⁹, wherein R⁷ andR⁸ are each independently hydrogen, halogen, hydroxy, carboxy,substituted or unsubstituted alkyl, substituted or unsubstitutedalkyloxy, substituted or unsubstituted aryl, substituted orunsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl or substituted orunsubstituted heterocycle, n is an integer of 1 to 10, R⁹ is —OR¹⁰ or—NR¹¹R¹², R¹⁰ is hydrogen, substituted or unsubstituted alkyl,substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl or substituted or unsubstituted heterocycle,R¹¹ and R¹² are each independently hydrogen, substituted orunsubstituted alkyl, substituted or unsubstituted alkyloxy, substitutedor unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedaryl, substituted or unsubstituted heteroaryl, substituted orunsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl orsubstituted or unsubstituted heterocycle.

Preferable is substituted arylalkyl, wherein a substituent on a ring ofthe substituted arylalkyl is carboxy, substituted or unsubstitutedcarbamoyl, substituted or unsubstituted alkylsulfonyl or substituted orunsubstituted sulfamoyl, substituted heteroarylalkyl, wherein asubstituent on a ring of the substituted heteroarylalkyl is carboxy,substituted or unsubstituted carbamoyl, substituted or unsubstitutedalkylsulfonyl or substituted or unsubstituted sulfamoyl or a grouprepresented by the formula: —(CR⁷R⁸)n-C(═O)—R⁹.

As a pharmaceutically acceptable salt of the present compound, thefollowing salts can be included.

As a basic salt, example includes alkali metal salt such as sodium saltor potassium salt; alkaline earth metal salt such as calcium salt ormagnesium salt; ammonium salt; aliphatic amine salt such astrimethylamine salt, triethylamine salt, dicyclohexylamine salt,ethanolamine salt, diethanolamine salt, triethanolamine salt, procainesalt, meglumine salt, diethanolamine salt or ethylenediamine salt;aralkylamine salt such as N,N-dibenzylethylenediamine salt orbenethamine salt; heterocyclic aromatic amine salt such as pyridinesalt, picoline salt, quinoline salt, or isoquinoline salt; quaternaryammonium salt such as tetramethylammonium salt, tetraethylammonium salt,benzyltrimethylammonium salt, benzyltriethylammonium salt,benzyltributylammonium salt, methyltrioctylammonium salt, ortetrabutylammonium salt; basic amino acid salt such as arginine salt orlysine salt or the like.

As an acidic salt, example includes inorganic acid salt such ashydrochloride, sulfate, nitrate, phosphate, carbonate,hydrogencarbonate, or perchlorate; organic acid salt such as acetate,propionate, lactate, maleate, fumarate, tartrate, malate, citrate orascorbate; sulfonate such as methanesulfonate, isethionate,benzenesulfonate or p-toluenesulfonate; acidic amino acid salt such asaspartate or glutamate or the like.

The term “solvate” means a solvate of a compound of the presentinvention or a pharmaceutically acceptable salt thereof, and exampleincludes alcohol (e.g., ethanol) solvate, hydrate or the like. Exampleof hydrate includes monohydrate, dihydrate or the like.

The term “inhibition”, as used herein, means that the present compoundinhibits work of EL.

The term “pharmaceutically acceptable”, as used herein, means being notharmful for prevention or treatment.

A general method for producing the present compound is exemplifiedbelow. Also extraction, purification and the like may be conducted in aprocedure performed in usual organic chemical experiment.

The compound represented by the Formula (I-1) can be synthesized by thefollowing method.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (I′-1), a knowncompound can be used, or a compound derived from a known compound by ausual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

Step 1

Step 1 is a process for preparing the compound represented by theFormula (I′-2) which comprises reacting the compound represented by theFormula (I′-1) with the compound represented by the Formula:CHR¹R²—COO-ak.

As a solvent, example includes N,N-dimethylformamide, dimethylsulfoxide,aromatic hydrocarbons (e.g., toluene, benzene, xylene or the like),saturated hydrocarbons (e.g., cyclohexane, hexane or the like),halogenated hydrocarbons (e.g., dichloromethane, chloroform,1,2-dichloroethane or the like), ethers (e.g., tetrahydrofuran,diethylether, dioxane, 1,2-dimethoxyethane or the like), esters (e.g.,methyl acetate, ethyl acetate or the like), ketones (e.g., acetone,methylethylketone or the like), nitriles (e.g., acetonitrile or thelike), alcohols (e.g., methanol, ethanol, t-butanol or the like), water,a mixed solvent thereof or the like.

As a base, example includes metal hydrides (e.g., sodium hydride or thelike), metal hydroxides (e.g., sodium hydroxide, potassium hydroxide,lithium hydroxide, barium hydroxide or the like), metal carbonates(e.g., sodium carbonate, calcium carbonate, cesium carbonate or thelike), metal alkoxides (e.g., sodium methoxide, sodium ethoxide,potassium t-butoxide or the like), sodium hydrogen carbonate, metalsodium, metal amide, organic amines (e.g., triethylamine,diisopropylethylamine, DBU, 2,6-lutidine or the like), pyridine, alkyllithiums (n-BuLi, sec-BuLi, tert-BuLi or the like) or the like.

Preferably, the reaction can be performed in a solvent of aromatichydrocarbons (e.g., toluene, benzene, xylene or the like) or ethers(e.g., tetrahydrofuran, diethylether, dioxane, 1,2-dimethoxyethane orthe like) with metal sodium or metal amide as a base. The reaction canbe performed at −78 to 30° C. for 0.5 to 12 hours.

As a compound represented by the Formula: CHR¹R²—COO-ak, exampleincludes butyl acetate or ethyl acetate.

Step 2

Step 2 is a process for preparing the compound represented by theFormula (I′-3) which comprises reacting the compound represented by theFormula (I′-2) with the compound represented by the Formula: R¹—NR³H.

As a solvent, a solvent described in Step 1 can be used. Preferably,N,N-dimethylformamide, dimethylsulfoxide or N-methyl-2-pyroridon can beused. The reaction can be performed under the conditions which do notuse a solvent by using microwave.

As a base, a base described in Step 1 can be used. Preferably, organicamines (e.g., triethylamine, diisopropylethylamine, DBU, pyridine,2,6-lutidine or the like) can be used.

The reaction can be performed at a temperature at which a solvent beingused is refluxed, for 0.5 to 12 hours.

The reaction can be performed at 80 to 200° C. for 5 minutes to 1 hourby using microwave. This reaction can be performed in a solventdescribed above or without any solvent.

As a compound represented by the Formula: R¹—NR³H, example includestert-butyl 3-(aminomethyl)benzoate hydrochloride or the like.

Step 3

Step 3 is a process for preparing the compound represented by theFormula (I-1) which comprises reacting the compound represented by theFormula (I′-3) with the compound represented by the Formula: R⁵—B(OH)₂in the presence of a palladium catalyst.

As a solvent, a solvent described in Step 1 can be used. Preferably,aromatic hydrocarbons (e.g., toluene, benzene, xylene or the like) orethers (e.g., tetrahydrofuran, diethylether, dioxane,1,2-dimethoxyethane or the like) can be used. The reaction can beperformed under the conditions which do not use a solvent by usingmicrowave.

As a base, a base described in Step 1 can be used. Preferably, metalcarbonates (e.g., sodium carbonate, calcium carbonate, cesium carbonateor the like) or organic amines (e.g., triethylamine,diisopropylethylamine, DBU, 2,6-lutidine or the like) can be used. Thereaction can be performed in the presence of palladium catalyst (e.g.,Pd(PPh₃)₄, PdCl₂, Pd(OAc)₂, Pd(dba)₂ or the like) and phosphine ligand(e.g., PPh₃, BINAP or the like) at a temperature at which a solventbeing used is refluxed, for 0.5 to 12 hours. The reaction can beperformed at 80 to 200° C. for 5 minutes to 1 hour by using microwave.This reaction can be performed in a solvent described above or withoutany solvent.

As a compound represented by the Formula: R⁵—B(OH)₂, example includesphenyl boronic acid or the like.

The compound represented by the Formula (II-1) can be synthesized by thesame scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (II′-1), aknown compound can be used, or a compound derived from a known compoundby a usual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

The compound represented by the Formula (III-1) can be synthesized bythe same scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (III′-1), aknown compound can be used, or a compound derived from a known compoundby a usual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

The compound represented by the Formula (IV-1) can be synthesized by thesame scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (IV′-1), aknown compound can be used, or a compound derived from a known compoundby a usual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

The compound represented by the Formula (V-1) can be synthesized by thesame scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (V′-1), a knowncompound can be used, or a compound derived from a known compound by ausual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

As an alternative general method for producing the present compound, thegroup represented by the Formula: —R⁵ can be introduced beforeintroduction of the group represented by the Formula: —C(R¹R²)—CO—NR³R⁴.

For example, it is explained below by employing Step 4 to 6.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (I′-4), a knowncompound can be used, or a compound derived from a known compound by ausual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

Step 4

Step 4 is a process for preparing the compound represented by theFormula (I′-2) which comprises reacting the compound represented by theFormula (I′-4) with the compound represented by the Formula:CHR¹R²—COO-ak.

The reaction can be performed under the conditions described in theabove Step 1.

Step 5

Step 5 is a process for preparing the compound represented by theFormula (I′-5) which comprises reacting the compound represented by theFormula (I′-2) with the compound represented by the Formula: R⁵—B(OH)₂in the presence of a palladium catalyst.

The reaction can be performed under the conditions described in theabove Step 3.

Step 6

Step 6 is a process for preparing the compound represented by theFormula (I-1) which comprises reacting the compound represented by theFormula (I′-5) with the compound represented by the Formula: R⁴—NR³H.

The reaction can be performed under the conditions described in theabove Step 2.

The compound represented by the Formula (II-1) can be synthesized by thesame scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (II′-4), aknown compound can be used, or a compound derived from a known compoundby a usual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

The compound represented by the Formula (III-1) can be synthesized bythe same scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (III′-4), aknown compound can be used, or a compound derived from a known compoundby a usual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

The compound represented by the Formula (IV-1) can be synthesized by thesame scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (IV′-4), aknown compound can be used, or a compound derived from a known compoundby a usual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

The compound represented by the Formula (V-1) can be synthesized by thesame scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (V′-4), a knowncompound can be used, or a compound derived from a known compound by ausual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

The compound represented by the Formula (I-1) can be synthesized by thefollowing method.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (I′-5), a knowncompound can be used, or a compound derived from a known compound by ausual method can be used. ak is C1 to C3 alkyl.

Step 7

Step 7 is a process for preparing the compound represented by theFormula (I′-6) which comprises hydrolyzing the compound represented bythe Formula (I′-5).

As a solvent, a solvent described in Step 1 can be used. Preferably,alcohols (e.g., methanol, ethanol, t-butanol or the like) can be used.

As a base, a base described in Step 1 can be used. Preferably, metalhydroxides (e.g., sodium hydroxide, potassium hydroxide, lithiumhydroxide, barium hydroxide or the like) can be used. The reaction canbe performed at −20 to 90° C. for 0.5 to 24 hours.

Step 8

Step 8 is a process for preparing the compound represented by theFormula (I-1) which comprises reacting the compound represented by theFormula (I′-6) with the compound represented by the Formula: R⁴—NR³H.

The reaction can be performed under the conditions described in theabove Step 2.

Preferably, a condensing agent (e.g., water soluble carbodiimide such asN,N-dicyclohexylcarbodiimide) and a catalyst such ashydroxybenzotriazole or hydroxysuccinimide can be used.

The compound represented by the Formula (II-1) can be synthesized by thesame scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (II′-5), aknown compound can be used, or a compound derived from a known compoundby a usual method can be used. ak is C1 to C3 alkyl.

The compound represented by the Formula (III-1) can be synthesized bythe same scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (III′-5), aknown compound can be used, or a compound derived from a known compoundby a usual method can be used. ak is C1 to C3 alkyl.

The compound represented by the Formula (IV-1) can be synthesized by thesame scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (IV′-5), aknown compound can be used, or a compound derived from a known compoundby a usual method can be used. ak is C1 to C3 alkyl.

The compound represented by the Formula (V-1) can be synthesized by thesame scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (V′-5), a knowncompound can be used, or a compound derived from a known compound by ausual method can be used. ak is C1 to C3 alkyl.

The compound represented by the Formula (I′-2) can be synthesized by thefollowing method.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (I′-7), a knowncompound can be used, or a compound derived from a known compound by ausual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

Step 9

Step 9 is a process for preparing the compound represented by theFormula (I′-2) which comprises reacting the compound represented by theFormula (I′-7) with the compound represented by the Formula: (ak-O)₂CO.

As a solvent, a solvent described in Step 1 can be used. Preferably,ethers (e.g., tetrahydrofuran, diethylether, dioxane or the like) can beused.

As a base, a base described in Step 1 can be used. Preferably, organicamines (e.g., triethylamine, diisopropylethylamine, DBU, 2,6-lutidine orthe like), pyridine or alkyl lithiums (n-BuLi, sec-BuLi, tert-BuLi orthe like) can be used.

The reaction can be performed at −78 to 30° C. for 0.5 to 24 hours.

As a compound represented by the Formula: (ak-O)₂CO, example includesdiethyl carbonate or the like.

The compound represented by the Formula (II′-2) can be synthesized bythe same scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (II′-7), aknown compound can be used, or a compound derived from a known compoundby a usual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

The compound represented by the Formula (III′-2) can be synthesized bythe same scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (III′-7), aknown compound can be used, or a compound derived from a known compoundby a usual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

The compound represented by the Formula (IV′-2) can be synthesized bythe same scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (IV′-7), aknown compound can be used, or a compound derived from a known compoundby a usual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

The compound represented by the Formula (V′-2) can be synthesized by thesame scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (V′-7), a knowncompound can be used, or a compound derived from a known compound by ausual method can be used. ak is C1 to C3 alkyl and Hal is halogen.

The compound represented by the Formula (III′-10) can be synthesized bythe following method.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (III′-8), aknown compound can be used, or a compound derived from a known compoundby a usual method can be used. Hal is halogen.

Step 10

Step 10 is a process for preparing the compound represented by theFormula (III′-9) which comprises reacting the compound represented bythe Formula (III′-8) with potassium thiocyanate.

As a solvent, a solvent described in Step 1 can be used. Preferably,halogenated hydrocarbons, acetic acid or water can be used.

As an oxidant, bromine or iodine can be used.

The reaction can be performed at −20 to 50° C. for 0.5 to 48 hours.

Step 11

Step 11 is a process for preparing the compound represented by theFormula (III′-10) which comprises halogenating the compound representedby the Formula (III′-9).

As a solvent, a solvent described in Step 1 can be used. Preferably,nitriles can be used.

As a halogenating agent, copper chloride (II) or copper bromide (II) canbe used.

The reaction can be performed at −20 to 90° C. for 0.5 to 48 hours.

The compound represented by the Formula (IV′-10) can be synthesized bythe same scheme as described above.

wherein each symbol in the above scheme has the same meaning as theabove, and as to the compound represented by the Formula (IV′-8), aknown compound can be used, or a compound derived from a known compoundby a usual method can be used. Hal is halogen.

Various substituents in the present compound can be introduced byreferring to (1) Alan R. Katriszly et al., Comprehensive HeterocyclicChemistry (2) Alan R. Katriszly et al., Comprehensive HeterocyclicChemistry II (3) RODD'S CHEMISTRY OF CARBON COMPOUNDS VOLUME IVHETEROCYCLIC COMPOUNDS or the like.

The present compound has excellent inhibitory activity on endotheliallipase. Therefore, it can be used for treatment or prevention of adisease concerning endothelial lipase, especially, disease such as lipidmetabolism abnormality, hyperlipidemia, diabetes, obesity,arteriosclerosis, atherosclerosis and/or syndrome X. It is particularlyuseful in treatment or prevention of hyperlipidemia, arteriosclerosis orlipid metabolism abnormality.

A compound used in the present invention can be orally or parenterallyadministered. When administered orally, the compound used in the presentinvention can be used in any dose form including normal formulations,for example, solid formulations such as a tablet, powder, granule,capsule or the like; aqueous formulations; oleaginous suspensions; orliquid formulations such as syrup or elixir. When administeredparenterally, the compound used in the present invention can be used asan aqueous or oleaginous suspension for injection or nasal solution. Inpreparation of such formulations, a conventional excipient, binder,lubricant, aqueous solvent, oleaginous solvent, emulsifying agent,suspending agent, preservative, stabilizer and the like can beoptionally used. Especially, using in a form of an oral formulation ispreferred.

A formulation of the compound used in the present invention can beproduced by combining (e.g., mixing) a therapeutically effective amountof the compound used in the present invention with a pharmaceuticallyacceptable carrier or diluent. Formulation of the compound used in thepresent invention can be produced by a known method using a well-knowneasily available ingredient.

A dose of the compound used in the present invention is differentdepending on an administration method, an age, a weight and thecondition of a patient, and a kind of a disease and, in the case of oraladministration, usually about 0.05 mg to 3000 mg, preferably about 0.1mg to 1000 mg per a day for adult person may be administered, ifnecessary, in divided doses. In addition, in the case of parenteraladministration, about 0.01 mg to 1000 mg, preferably about 0.05 mg to500 mg per a day for adult person may be administered. Inadministration, it can be used together with other therapeutic agents.

The present invention is further explained by the following Examples,which are not intended to limit the scope of the present invention.

The NMR spectrum or LC/MS data of the present compound and itsintermediate was described below. LC/MS was measured under any one ofthe following three conditions.

Method A:

Luna 5μ C18(2) 100 A, 50×4.6 mm (made by Phenomenex) was used formeasurement.

A three minute linear gradient was run from 10:90-100:0 ofacetonitrile/water (0.1% formic acid) with 3 ml/min of flow rate, andacetonitrile was passed for 1 minute.

Method C:

Shim-pack XR-ODS 50 L×3.0 (made by Shimazu) was used for measurement.

A three minute linear gradient was run from 10:90-100:0 ofacetonitrile/water (0.1% formic acid) with 1.6 ml/min of flow rate, andacetonitrile was passed for 30 seconds.

Method D:

Shim-pack XR-ODS 50 L×3.0 (made by Shimazu) was used for measurement.

A eight minute linear gradient was run from 10:90-100:0 ofacetonitrile/water (0.1% formic acid) with 1.6 ml/min of flow rate.

The terms used in the Examples are as follows.

NaHMDS: Sodium Bis(trimethylsilyl)amide

NMP: N-Methyl-2-pyrrolidoneTFA: Trifluoroacetic acid

THF: Tetrahydrofuran DMF: Dimethylformamide

WSCD: 1-Ethyl-3-(3-dimethyl aminopropyl) carbodiimideBOC: t-Butoxycarbonyl groupBn: Benzyl groupLHMDS: lithium hexamethyldisilazideHATU: O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphatePd₂(dba)₃: BIS(Dibenzylideneacetone)palladiumMCPBA: META-Chloroperbenzoic acidX-Phos: 2-Dicyclohexylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl

NCS: N-Chlorosuccinimide

Fe(acac)₃: Ferric acetylacetonateH-Gly-OtBu: Glycine tert-butyl ester

Example 1

To a solution of 2M NaHMDS THF solution (111 mL, 211 mmol) in anhydroustoluene (375 mL) was added ethyl acetate (11.30 mL, 116 mmol) undernitrogen atmosphere at −60° C. for 10 minutes. It was stirred for 1 hourat −60° C. To the solution was dropped a solution of 6-bromo-2-chlorobenzothiazole1 (25 g, 101 mmol) in an anhydrous toluene (125 ml). Afterdropping, it was stirred at 0° C. for 2 hours.

To the reaction mixture were added 1M hydrochloric acid and ethylacetate. The mixture was extracted. The organic layer was washed withbrine, dried with magnesium sulfate. The solvent was evaporated underreduced pressure. The residue was washed with a mixed solvent of hexaneand diisopropyl ether to give Compound 2 (27.1 g, 90%) as a yellowsolid.

Compound 2; ¹H-NMR (CDCl₃) δ: 1.31 (t, J=7.2, Hz 3.0, 3H), 4.15 (s, 2H),4.26 (q, J=7.2 Hz, 2H), 7.57 (dd, J=8.7, 1.8 Hz, 1H), 7.86 (d, J=9.0 Hz,1H), 8.01 (d, J=1.8 Hz, 1H)

Compound 2 (5 g, 16.7 mmol) was dissolved in NMP (50 ml). To thesolution were added tert-butyl 3-(aminomethyl)benzoate hydrochloride(4.9 g, 20 mmol) and Et₃N (3.5 ml, 25 mmol). The mixture was stirred at170° C. for 15 minutes under microwave irradiation. To the reactionmixture were added 1M hydrochloric acid and ethyl acetate. Afterextraction, the organic layer was washed with brine and dried overmagnesium sulfate. The solvent was evaporated under reduced pressure.The residue was purified with chromatography to give Compound 3 (4.9 g,64%).

Compound 3; ¹H-NMR (DMSO-d₆) δ: 1.51 (s, 9H), 4.14 (s, 2H) 4.40 (d,J=5.7 Hz, 2H), 7.45 (t, J=7.2 Hz, 1H) 7.54 (d, J=7.8 Hz, 1H), 7.64 (d,J=10.8 Hz, 1H), 7.76-7.82 (m, 3H), 7.89 (d, J=8.4 Hz, 1H), 8.36 (s, 1H),8.95 (t, J=6.0 Hz) 1H)

To a solution of Compound 3 (60 mg, 0.13 mmol) in anhydrous 1,4-dioxane(4 mL) solution were added phenyl boronic acid (24 mg, 0.20 mmol),Pd(PPh₃)₄. (8 mg) and 2N Na₂CO₃ solution (200 μl). It was stirred at140° C. for 15 minutes under microwave irradiation. To the reactionmixture was added 1M hydrochloric acid and ethyl acetate. Afterextraction, the organic layer was washed with saturated sodiumbicarbonate solution and brine, respectively and dried over sodiumsulfate. The solvent was evaporated under reduced pressure. The residuewas purified with chromatography to give Compound 4 (37 mg, 62%).

Compound 4; ¹H-NMR (DMSO-d₆) δ: 1.52 (s, 9H), 4.15 (s, 2H), 4.41 (d,J=6.1 Hz, 2H), 7.37-7.57 (m, 5H), 7.74-7.86 (m, 4H), 7.92 (s, 1H), 8.02(d, J=8.6 Hz, 1H), 8.38 (d, J=1.5 Hz, 1H), 8.95 (t, J=6.1 Hz, 1H)

To a solution of Compound 4 (37 mg, 0.08 mmol) in dichloromethane (1 ml)was added trifluoroacetic acid (1 ml). It was stirred at roomtemperature for 2 hours. The solvent was evaporated under reducedpressure. It was crystallized with diethyl ether to give Compound(II-1-1) (29 mg 88%).

Compound (II-1-1); ¹H-NMR (DMSO-d₆) δ: 4.15 (s, 2H), 4.41 (d, J=6.1 Hz,2H) 7.37-7.57 (m, 5H), 7.74-7.86 (m, 4H), 7.92 (s, 1H), 8.02 (d, J=8.6Hz, 1H), 8.38 (d, J=1.5 Hz, 1H), 8.95 (t, J=6.1 Hz, 1H), 12.96 (br s,1H).

Example 2

To a solution of Compound 3 (200 mg, 0.43 mmol) in ethyl acetate (3 mL)were added copper triflate benzene complex (22 mg, 0.043 mmol), naphtoicacid (149 mg, 0.87 mmol), phenol (82 mg, 0.87 mmol) and cesium carbonate(282 mg, 0.87 mmol). It was stirred for 140° C. for 3 hours undermicrowave irradiation. To the reaction mixture were added 1Mhydrochloric acid and ethyl acetate. After extraction, the organic layerwas washed with brine and dried over sodium sulfate. The solvent wasevaporated under reduced pressure. The residue was purified withchromatography to give Compound 5 (26 mg, 13%).

Compound 5; ¹H-NMR (DMSO-d₆) δ: 1.52 (s, 9H), 4.10 (s, 2H), 4.40 (d,J=6.1 Hz, 2H), 7.04 (d, J=8.1 Hz, 2H) 7.13-7.20 (m, 2H), 7.38-7.48 (m,3H), 7.54 (d, J=7.6 Hz, 1H), 7.72 (d, J=2.5 Hz, 1H), 7.83 (d, J=7.6 Hz,1H), 7.90 (s, 1H), 7.95 (d, J=8.6 Hz, 1H), 8.92 (t, J=5.8 Hz, 1H).

Compound (II-1-2) (23 mg, 100%) was obtained in accordance with the samemanner as Example 1.

Compound (II-1-2); ¹H-NMR (DMSO-d₆) δ: 4.10 (s, 2H), 4.40 (d, J=6.1 Hz,2H) 7.04 (d, J=8.1 Hz, 2H), 7.13-7.20 (m, 2H), 7.38-7.48 (m, 3H), 7.54(d, J=7.6 Hz, 1H) 7.72 (d, J=2.5 Hz, 1H), 7.83 (d, J=7.6 Hz, 1H), 7.90(s, 1H), 7.95 (d, J=8.6 Hz, 1H), 8.92 (t, J=5.8 Hz, 1H), 12.96 (br s,1H).

Example 3

To a solution of 5-bromo-2-methylbenzothiazole 6 (6.5 g, 28.5 mmol) inanhydrous THF (260 mL) was dropped 1M LHMDS THF solution (59.8 mL, 59.8mmol) at −60° C. under nitrogen atmosphere. After stirred at −60 to −78°C. for 80 minutes, diethyl carbonate (3.80 mL, 31.3 mmol) was added tothe solution. It was stirred at 0° C. for 1 hour.

To the reaction mixture were added 1M hydrochloric acid and ethylacetate. After extraction, the organic layer was washed with saturatedsodium bicarbonate solution and brine, respectively and dried oversodium sulfate. The solvent was evaporated under reduced pressure. Theresidue was washed with hexane to give Compound 7 (7.19 g, 84%) as abrown solid.

Compound 7; ¹H-NMR (CDCl₃) δ: 1.31 (t, J=7.1 Hz, 3H), 4.17 (s, 2H), 4.26(q, J=7.1 Hz, 2H), 7.50 (dd, J=8.6, 2.0 Hz, 1H), 7.74 (d, J=8.6 Hz, 1H),8.16 (d, J=2.0 Hz, 1H).

The compound 8 (984 mg, 43%) was obtained in accordance with the samemanner as Example 1.

Compound 8; ¹H-NMR (CDCl₃) δ: 1.58 (s, 9H), 4.11 (s, 2H) 4.55 (d, J=6.1Hz, 2H), 7.37 (t, J=7.6 Hz, 1H) 7.45 (d, J=7.6 Hz, 1H), 7.50-7.53 (m,2H), 7.73 (d, J=8.1 Hz, 1H), 7.89-7.90 (m, 2H), 8.14 (s, 1H).

The compound 9 (45 mg, 66%) was obtained in accordance with the samemanner as Example 1.

Compound 9; ¹H-NMR (CDCl₃) δ: 1.56 (s, 9H), 4.15 (s, 2H) 4.57 (d, J=6.1Hz, 2H), 7.34-7.39 (m, 3H), 7.45-7.61 (m, 3H), 7.69 (s, 1H), 7.78 (d,J=7.6 Hz, 1H), 7.87-7.91 (m, 3H), 7.95 (s, 1H).

The compound (II-1-3) (29 mg, 88%) was obtained in accordance with thesame manner as Example 1.

Compound (II-1-3); ¹H-NMR (DMSO-d₆) δ: 4.17 (s, 2H), 4.41 (d, J=5.6 Hz,2H), 7.36 (d, J=8.1 Hz, 1H), 7.44-7.50 (m, 2H), 7.55 (d, J=7.6 Hz, 1H),7.65 (t, J=7.6 Hz, 1H), 7.76 (t, J=7.6 Hz, 1H), 7.82-7.91 (m, 4H), 8.12(d, J=8.1 Hz, 1H), 8.94 (t, J=5.8 Hz, 1H), 12.95 (br s, 1H).

Example 4

To a solution of copper chloride (II) (1.90 g, 14.10 mmol) in anhydrousdimethylformamide (5 ml) were dropped under ice-cooling isoamyl nitrite(2.37 ml, 17.62 mmol) and a suspension of Compound 10 (3 g, 11.75 mmol)in anhydrous dimethylformamide (10 ml), respectively. It was stirred at50° C. for 2 hours. To the reaction mixture were added saturationammonium chloride solution (50 ml) and ethyl acetate (50 ml). Afterextraction, the organic layer was washed with brine (40 ml) three timesand dried over magnesium sulfate. The solvent was evaporated underreduced pressure. The residue was purified with silicagel chromatography(n-hexane:ethyl acetate=5:1) to give Compound 11 (1.62 g, 50%) as awhite solid.

Compound 11; ¹H-NMR (CDCl₃): δ (ppm) 1.49 (s, 9H), 2.82 (t, J=5.6 Hz,2H), 3.73 (t, J=5.6 Hz, 2H), 4.55 (s, 2H).

1.9 M NaHMDS/THF solution (1.47 ml, 2.73 mmol) was diluted with absoluteTHF (1.5 ml) at −60° C. To the solution was dropped acetonitrile (95 μl,1.82 mmol). It was stirred for 30 minutes. To the solution a solution ofCompound 11 (250 mg, 0.91 mmol) in absolute THF (2 ml). It was stirredat room temperature for 1 hour. It was diluted with 2M HCl (3 ml) andextracted with ethyl acetate (5 ml). The oil layer was washed with brine(5 ml). The solvent was evaporated under reduced pressure. The residuewas purified with silicagel chromatography (n-hexane:ethyl acetate=3:1)to give Compound 12 (150 mg, 59%) as red oil.

Compound 12; ¹H-NMR (DMSO-d₆): δ (ppm) 1.42 (s, 9H), 2.75 (t, J=5.6 Hz,2H), 3.63 (t, J=5.6 Hz, 2H), 4.50 (s, 2H), 4.58 (s, 2H)

To a solution of Compound 12 (120 mg, 0.430 mmol) in dichloromethane(1.2 ml) was added TFA (0.50 ml, 6.44 mmol) at 0° C. It was stirred for2 hours. Dichloromethane and trifluoroacetic acid were evaporated underreduced pressure. The residue was dissolved in anhydrous DMF (1.5 ml).To the solution were added triethyl amine (0.12 ml, 0.86 mmol) andbenzyl bromide (51 μl, 0.43 mmol). It was stirred at room temperaturefor 2.5 hours. The reaction mixture was diluted with sat. NaHCO₃ aq. (5ml) and extracted with ethyl acetate (10 ml). The organic layer waswashed with sat. NaHCO₃ aq. (5 ml). The solvent was evaporated underreduced pressure. The residue was purified with silicagel chromatography(chloroform:methanol=99:1) to give Compound 13 (77.5 mg, 67%) as yellowoil.

Compound 13; ¹H-NMR (DMSO-d₆): δ (ppm) 2.73 (m, 2H), 2.89 (m, 2H), 3.64(s, 2H), 3.70 (s, 2H) and 4.47 (s, 2H), 7.29-7.37 (m, 5H).

To a solution of Compound 13 (67 mg, 0.249 mmol) in ethanol was added 5MNaOH solution (0.15 ml, 0.746 mmol). It was heated under reflux andstirred for 1 hour. The solvent was evaporated under reduced pressure.Compound 14 (70 mg, 95%) was obtained as brown oil.

Compound 14; LC/MS Rt=0.60 min, MS:288.90, method:A

To a solution of Compound 14 (77 mg, 0.248 mmol) in DMF (1.5 ml) wereadded Et₃N (0.206 ml, 1.489 mmol), HOBt (67.1 mg, 0.496 mmol), WSCD HCl(95 mg, 0.496 mmol) and tert-butyl 3-(aminomethyl)benzoate hydrochloride(121 mg, 0.496 mmol). It was stirred overnight at room temperature. Thereaction mixtures was diluted with H₂O (5 ml) and extracted with ethylacetate (10 ml). The oil layer was washed with H₂O (5 ml) and brine (5ml), respectively And dried over magnesium sulfate. The solvent wasevaporated under reduced pressure. The residue was purified withsilicagel chromatography (chloroform:methanol=50:1) to give Compound 15(20 mg, 17%) as tan oil.

Compound 15; LC/MS Rt=2.38 min, MS:478.20, method:A

To a solution of Compound 15 (20 mg, 0.042 mmol) in dichloromethane (1.0ml) was added TFA (500 μl, 6.49 mmol). It was stirred at roomtemperature for 1 hour. The solvent was evaporated under reducedpressure. The residue was purified with reverse phase chromatography(H₂O-MeCN, 5 to 95% MeCN/15 min) to give Compound (II-1-4) (8.7 mg, 49%)as a white solid.

Compound (II-1-4); ¹H-NMR (DMSO-d₆) δ: 2.68-2.82 (m, 4H), 3.61 (s, 3H),3.70 (s, 2H), 3.88 (s, 2H), 4.36 (d, J=5.6 Hz, 2H), 7.21-7.55 (m, 7H),7.75-7.90 (m, 2H), 8.80 (t, J=5.6 Hz, 1H).

Example 5

To a suspension of copper chloride (II) (9.15 g, 68.1 mmol) in anhydrousacetonitrile (100 ml) were dropped under ice-cooling isoamyl nitrite(11.46 ml, 85 mmol) and a suspension of Compound 16 (10 g, 56.7 mmol) inanhydrous acetonitrile (100 ml), respectively. It was stirred at 50° C.for 3 hours. The insoluble was filtered out. The solvent was evaporatedunder reduced pressure. To the residue were added ethyl acetate (200 ml)and 1M HCl (100 ml). The mixture was extracted. The organic layer waswashed with brine (100 ml) and dried over magnesium sulfate. The solventwas evaporated under reduced pressure. The residue was purified withsilicagel chromatography (n-hexane:ethyl acetate=99:1) to give Compound17 (2.5 g, 23%) as a white solid.

Compound 17; ¹H-NMR (DMSO-d₆): δ (ppm) 7.34-7.44 (m, 1H), 7.44-7.50 (m,2H), 7.86-7.94 (m, 2H), 8.12 (s, 1H).

1.9 M NaHMDS/THF solution (8.07 ml, 15.33 mmol) was diluted withabsolute THF (10 ml) at −60° C. To the solution was dropped acetonitrile(531 μl, 10.22 mmol). It was stirred for 30 minutes. To the mixture wasdropped the solution of Compound 17 (1 g, 5.11 mmol) in absolute THF (10ml). It was stirred for 1 hour at 0° C. The mixture was diluted with 2MHCl (10 ml) and extracted with ethyl acetate (50 ml). The oil layer waswashed with brine (50 ml). The solvent was evaporated under reducedpressure. The residue was purified with silicagel chromatography(n-hexane:ethyl acetate=4:1) to give Compound 18 (740 mg, 72%) as agreen solid.

Compound 18; ¹H-NMR (DMSO-d₆): δ (ppm) 4.63 (s, 2H), 7.33-7.40 (m, 1H),7.42-7.51 (m, 2H), 7.90-8.00 (m, 2H), 8.13 (s, 1H).

To a solution of Compound 18 (130 mg, 0.649 mmol) in EtOH (1.5 ml) wasadded 5 M NaOH solution (0.389 ml, 1.947 mmol). It was heated underreflux for 1 hour, diluted with 1M HCl aqueous solution (5 ml), andextracted with chloroform (10 ml) five times. The organic layer wasdried over magnesium sulfate. The solvent was evaporated under reducedpressure. The residue was purified with silicagel chromatography(CHCl₃:MeOH:AcOH=10:1:0.1) to give Compound 19 (77.2 mg, 54%) as brownoil.

Compound 19; ¹H-NMR (DMSO-d₆): δ (ppm) 4.13 (s, 2H), 7.30-7.37 (m, 1H),7.39-7.47 (m, 2H), 7.90-7.97 (m, 2H), 8.04 (s, 1H), 12.81 (brs, 1H)

To a solution of Compound 19 (60 mg, 0.274 mmol) in DMF (1 ml) wereadded triethylamine (0.19 ml, 1.368 mmol), WSCD-HCl (79 mg, 0.410 mmol),HOBt (56 mg, 0.410 mmol) and tert-butyl 3-(aminomethyl)benzoatehydrochloride (133 mg, 0.547 mmol). It was stirred at room temperaturefor 12 hours. It was diluted with 1M HCl aqueous solution (2.0 ml) andextracted with ethyl acetate (10 ml). The oil layer was washed with H₂O(5 ml) and brine (5 ml), respectively and dried over magnesium sulfate.The solvent was evaporated under reduced pressure. The residue waspurified with silicagel chromatography (n-hexane:ethyl acetate=1:1) togive Compound 20 (61.4 mg, 55%) as yellow amorphous.

Compound 20; ¹H-NMR (DMSO-d₆) δ: 1.53 (s, 9H), 4.05 (s, 2H) 4.40 (d,J=5.6 Hz, 2H), 7.30-7.37 (m, 1H), 7.39-7.49 (m, 3H), 7.55 (d, J=7.6 Hz,1H), 7.76-7.85 (m, 2H), 7.93 (d, J=7.6 Hz, 2H), 8.00 (s, 1H), 8.87 (t,J=5.6 Hz, 1H).

To a solution of Compound 20 (58 mg, 0.142 mmol) in dichloromethane (1.0ml) was added TFA (0.328 ml, 4.26 mmol). It stirred at room temperaturefor 2 hours. The solvent was evaporated under reduced pressure. Theobtained yellow solid was suspended in ethyl acetate (5 ml). It wasstirred for 1 hour. The residue was filtered to give Compound (I-1-1)(33.3 mg, 67%) as a white solid.

Compound (1-1-1); ¹H-NMR (DMSO-d₆) δ: 4.05 (s, 2H), 4.40 (d, J=6.1 Hz,2H) 7.33 (dd J=7.1, 8.1 Hz, 1H), 7.40-7.49 (m, 3H), (d, J=7.6 Hz, 1H),7.83 (d, J=7.6 Hz, 1H), 7.88-7.96 (m, 3H), 8.00 (s, 1H), 8.87 (t, J=6.1Hz, 1H).

Example 6

To a solution of Compound 2 (20 g, 67 mmol) in anhydrous 1,4-dioxane(200 mL) were added TETRAKIS(TRIPHENYLPHOSPHINE) PALLADIUM (0) (5.39 g,4.66 mmol), PHENYLBORONIC ACID (9.75 g, 80 mmol) and K₃PO₄ (35.4 g, 167mmol) at room temperature. It was heated under reflux for 6 hours. Thereaction mixture was cooled to room temperature. To the mixture wereadded 1M hydrochloric acid and ethyl acetate. The mixture was extracted.The organic layer was washed with brine and dries over sodium sulfate.The solvent was evaporated under reduced pressure. The obtained residuewas purified with chromatography to give Compound 21 (16.1 g, 81%) as ayellow solid.

Compound 21; ¹H-NMR (CDCl₃) 6:1.31 (t, J=6.9 Hz, 3H), 4.19 (s, 2H), 4.27(q, J=7.2 Hz, 2H), 7.38 (t, J=7.5 Hz, 1H), 7.48 (t, J=7.2 Hz, 2H),7.63-7.73 (m, 3H), 8.06 (m, 2H)

To a solution of Compound 21 (5 g, 16.8 mmol) in anhydroustetrahydrofran (35 mL) were added 2N NaOH solution (11 mL, 20 mmol). Itwas stirred at room temperature for 40 minutes. After the end of thereaction, n-hexane was added to the solution. The insoluble residue wascollected by filtration. The obtained solid was washed with ethylacetate. The obtained product was dried under reduced pressure to giveCompound 22 (4.9 g, quant) as a yellows solid.

To a solution of Compound 22 (2 g, 6.87 mmol) in anhydrousdimethylformamide (20 ml) were added under nitrogen atmospheretert-butyl 2-aminoacetate hydrochloride (1.38 g, 8.24 mmol), pyridine(2.78 ml, 34.3 mmol) and HATU (3.13 g, 8.24 mmol) at room temperature.It was stirred for 4 hours. To the reaction mixture were added 1Mhydrochloric acid and ethyl acetate. The mixture was extracted. Theorganic layer was washed with brine and dried over sodium sulfate. Thesolvent was evaporated under reduced pressure. The obtained residue waspurified with chromatography to give Compound 23 (1.63 g, 62%).

Compound 23; ¹H-NMR (CDCl₃) δ: 1.46 (s, 9H), 4.01 (d, J=5.1 Hz, 2H),4.13 (s, 2H), 7.38 (d, J=6.6 Hz, 1H), 7.48 (t, J=7.2 Hz, 2H), 7.64 (d,J=6.9 Hz, 2H), 7.72 (m, 1H), 8.06-8.10 (m, 2H)

To a solution of Compound 23 (1.6 g, 4.18 mmol) in anhydrousdichloromethane (5 mL) was added trifluoroacetic acid (5 ml). It wasstirred at room temperature for 2 hours. The solvent was evaporatedunder reduced pressure. The obtained residue was crystallized withdiethyl ether to give Compound 24 (1.12 g, 82%).

Compound 24; ¹H-NMR (DMSO-d₆) δ: 3.85 (d, Hz J=5.7, 2H), 4.15 (s, 2H),7.39 (d, J=6.9 Hz, 1H), 7.50 (t, J=7.8 Hz, 2H), 7.74-7.81 (m, 3H), 8.02(d, J=8.7 Hz, 1H), 8.38 (s, 2H), 8.71 (m, 1H)

To a solution of Compound 24 (1.0 g, 3.06 mmol) in dimethylformamide (10ml) were added at room temperature under nitrogen atmosphere2-aminoacetonitrile hydrochloride (340 mg, 3.68 mmol), HATU (1.4 g, 3.68mmol) and Et₃N (1.27 mL, 9.2 mmol). It was stirred for 3 hours. Afterthe end of the reaction, 1M hydrochloric acid and ethyl acetate wereadded to the reaction mixture. It was extracted. The organic layer waswashed with 10% sodium bicarbonate and water, respectively and driedover sodium sulfate. The solvent was evaporated under reduced pressure.The obtained residue was purified with chromatography to give Compound(II-2-1) (540 mg, 48%) as a white solid.

Compound (II-2-1); ¹H-NMR (DMSO-d₆) δ: 3.84 (d, J=5.7 Hz, 2H), 4.17 (d,J=5.4 Hz, 4H) 7.39 (t, J=7.5 Hz, 1H), 7.50 (t, J=7.2 Hz, 2H), 8.02 (d,J=8.4 Hz, 1H), 8.38 (s, 1H), 8.69-8.75 (m, 2H)

Example 7

To a solution of 5-bromo-2-methylbenzothiazole 6 (1.3 g, 5.70 mmol) in1,4-dioxane (13 mL) were added at room temperature under nitrogenatmosphere sodium salt of thiophenol (0.828 g, 6.27 mmol), xantphos(0.330 g, 0.570 mmol) and Pd₂(dba)₃ (0.261 g, 0.285 mmol). It wasstirred for 30 minutes at 140° C. under microwave irradiation. Thereaction mixture was poured into water and extracted with ethyl acetate.The obtained organic layer was washed with saturated aqueous sodiumbicarbonate and brine, respectively and dried over magnesium sulfate.The solvent was evaporated under reduced pressure. The obtained residuewas purified with silicagel chromatography (n-hexane:ethyl acetate) togive Compound 25 (2.34 g, 9.09 mmol, 87%) as a yellow liquid.

Compound 25; ¹H-NMR (CDCl₃) δ: 2.82 (s, 3H), 7.25-7.39 (m, 6H), 7.74 (d,J=8.6 Hz, 1H), 7.89 (d, J=1.5 Hz, 1H).

To a solution of Compound 25 (2.34 g, 9.09 mmol) in dichloromathene (50mL) was added little by little mCPBA (5.07 g, 19.09 mmol). It wasstirred under ice-cooling for 2 hours. After the end of the reaction,the reaction mixture was poured into saturated aqueous sodiumbicarbonate solution and extracted with ethyl acetate. The organic layerwas washed with 10% aqueous sodium thiosulfate solution and brine,respectively and dried over sodium sulfate. The solvent was evaporatedunder reduced pressure. The obtained solid was washed with a mixedsolvent of ethyl acetate and isopropyl ether to give Compound 26 (2.28g, 7.88 mmol, 87%) as a white solid.

Compound 26; ¹H-NMR (CDCl₃) δ: 2.86 (s, 3H), 7.48-7.58 (m, 3H),7.89-7.99 (m, 4H), 8.52 (d, J=1.0 Hz, 1H).

Example 8

To a solution of Compound 27 (10.3 g, 62.7 mmol) in 2-propanol (300 mL)was added at room temperature under nitrogen atmosphere N-chlorosuccinimide (8.79 g, 65.9 mmol). It was stirred at room temperature for2 hours. After the end of the reaction, the reaction mixture was cooledto room temperature and poured into saturated aqueous sodiumbicarbonate. It was extracted twice with dichloromethane. The organiclayer was washed with brine and dried over sodium sulfate. The solventwas evaporated under reduced pressure. The obtained residue was purifiedwith silicagel chromatography (n-hexane:ethyl acetate) to give Compound28 (4.95 g, 24.92 mmol, 40%) as a thin orange solid.

Compound 28; ¹H-NMR (CDCl₃) δ: 2.77 (s, 3H), 4.11 (s, 2H), 6.88 (d,J=8.6 Hz, 1H), 7.63 (d, J=8.6 Hz, 1H).

A solution of Compound 28 (0.9 g, 4.53 mmol) in concentratedhydrochloric acid (5 mL) was diluted with water (5 ml). To the solutionwas dropped under ice-cooling a solution of sodium nitrite (344 mg, 4.98mmol) in water (5 mL). It was stirred for 30 minutes. To the solutionwas dropped slowly a solution of potassium iodide (2707 mg, 16.31 mmol)in water (25 mL). It was stirred at room temperature for 1 hour. Thereaction mixture was neutralized under ice-cooling with saturatedaqueous sodium bicarbonate and extracted with chloroform. The organiclayer was washed with a 10% aqueous solution of sodium thiosulfate andbrine, respectively and dried over magnesium sulfate. The solvent wasevaporated under reduced pressure. The obtained residue was purifiedwith silicagel chromatography (n-hexane:ethyl acetate) to give Compound29 (740 mg, 2.391 mmol, 53%) as a white solid.

Compound 29; LC/MS/Rt=2.54 min, MS:309.80 (M+1), method:C

To a solution of Compound 29 (740 mg, 2.391 mmol) in 1,4-dioxane (10 mL)and water (2.0 mL) at room temperature under nitrogen atmosphere phenylboronic acid (364 mg, 2.99 mmol), tetrakis(triphenylphosphine)palladium(276 mg, 0.239 mmol) and sodium bicarbonate (502 mg, 5.98 mmol). Afterthat, It was stirred at 100° C. for for 15 minutes under microwaveirradiation. After the end of the reaction, ethyl acetate was added tothe mixture. The organic layer was purified with silicagelchromatography (n-hexane:ethyl acetate) to give Compound 30 (588 mg,2.264 mmol, 95%).

Compound 30; LC/MS/Rt=2.56 min, MS:260.0 (M+1), method:C

Example 9

To a solution of 5-amino-2-methyl benzothiazole 31 (10 g, 60.9 mmol) in2-propanol (200 mL) was added at room temperature under nitrogenatmosphere N-bromo succinimide (23.84 g, 134 mmol). It was stirred at65° C. for 20 minutes. Furthermore, N-bromo succinimide (10.84 g, 60.9mmol) was added to the reaction mixture. It was stirred at 65° C. for 30minutes. The reaction mixture was poured into saturated aqueous sodiumbicarbonate and extracted with dichloromethane. The organic layer waswashed with brine and dried over sodium sulfate. The solvent wasevaporated under reduced pressure. The obtained residue was purifiedwith silicagel chromatography (n-hexane:ethyl acetate) to give Compound32 (12.15 g, 37.7 mmol, 62%) as a solid.

Compound 32; ¹H-NMR (CDCl₃) δ: 2.84 (s, 3H), 4.71 (br s, 2H), 7.84 (s,1H).

To a solution of Compound 32 (12.15 g, 37.7 mmol) in 1,4-dioxane (120mL) and water (30 mL) at room temperature under nitrogen atmospherephenyl boronic acid (5.75 g, 47.2 mmol),tetrakis(triphenylphosphine)palladium (4.36 g, 3.77 mmol) and sodiumcarbonate (8.00 g, 75 mmol). Then, it was heated under reflux for 7hours. After the end of the reaction, the mixture was poured into waterand extracted with a mixed solvent of ethyl acetate and THF. The organiclayer was washed with brine and dried over magnesium sulfate. Thesolvent was evaporated under reduced pressure. The obtained residue wascrystallized with ethyl acetate and n-hexane to give Compound 33 (9.6 g,30.1 mmol, 80%) as a solid.

Compound 33; ¹H-NMR (DMSO-d₆) δ: 2.78 (s, 3H), 4.84 (br s, 2H),7.41-7.53 (m, 5H), 7.65 (s, 1H).

To a solution of Compound 33 (8 g, 25.06 mmol) in THF (40 mL) andmethanol (40 mL) were added at room temperature under nitrogenatmosphere Pd/C (10%, water) (13.34 g, 6.27 mmol). To the solution wasadded continuously ammonium formates (15.80 g, 251 mmol). The reactionmixture stirred at 50° C. for 2 hours. To the mixture was added Pd/C(10%, water) (13.34 g, 6.27 mmol). It was stirred at 50° C. for 4 hours.The reaction mixture was cooled to room temperature. To the mixture wasadded ethyl acetate. The reaction mixture was filtered with celite andconcentrated under reduced pressure. The obtained residue was dilutedwith water. It was extracted with ethyl acetate. The organic layer wasdried over magnesium sulfate. The solvent was evaporated under reducedpressure. The obtained solid was washed with ethyl acetate and n-hexaneto give Compound 34 (3.16 g, 13.15 mmol, 53%) as a brown solid.

Compound 34; ¹H-NMR (DMSO-d₆) δ: 2.72 (s, 3H), 4.86 (br s, 2H), 7.26 (s,1H), 7.35-7.40 (m, 1H), 7.45-7.49 (m, 4H), 7.57 (s, 1H).

To a solution of isoamyl nitrite (1.707 mL, 12.17 mmol) in acetonitrile(40 mL) was added under ice-cooling and nitrogen atmosphere CuBr (1.397g, 9.74 mmol). After that, Compound 34 (1.95 g, 8.11 mmol) was added tothe solution little by little. It was stirred under ice-cooling for 20minutes. After that, the mixture stirred at 50° C. for further 2 hours.The reaction mixture was poured into 0.1M HCl aqueous solution andextracted with ethyl acetate. The organic layer was washed withsaturated aqueous sodium bicarbonate and brine, respectively and driedover magnesium sulfate. The solvent was evaporated under reducedpressure. The obtained residue was purified with silicagelchromatography (n-hexane:ethyl acetate) to give Compound 35 (1.005 g,3.30 mmol, 41%) as a solid.

Compound 35; ¹H-NMR (CDCl₃) δ: 2.86 (s, 3H), 7.40-7.46 (m, 5H), 7.76 (s,1H), 8.25 (s, 1H).

To a solution of Compound 35 (400 mg, 1.315 mmol) in NMP (1 mL) at roomtemperature under nitrogen atmosphere pyrazole (134 mg, 1.972 mmol),Fe(acac)₃ (139 mg, 0.394 mmol), copper oxide (II) (20.92 mg, 0.263 mmol)and cesium carbonate (857 mg, 2.63 mmol). It was stirred at 180° C. for30 minutes under microwave irradiation. Furthermore, it was stirred at190° C. for 1 hour under microwave irradiation. The reaction mixture waspoured into water and extracted with ethyl acetate. The organic layerwas washed with brine and dried over sodium sulfate. The solvent wasevaporated under reduced pressure. The obtained residue was purifiedwith silicagel chromatography (n-hexane:ethyl acetate) to give Compound36 (150 mg, 0.515 mmol, 39%).

Compound 36; LC/MS Rt=2.21 min, MS:292.050 (M+1), method:C

Example 10

To a solution of Compound 37 (300 mg, 1.248 mmol) and triethyl amine(0.260 mL, 1.872 mmol) in dichloromethane (6 mL) was added undernitrogen atmosphere and ice-cooling methane sulfonyl chloride (0.107 mL,1.373 mmol). It was stirred at room temperature for 5 hours. To thesolution were added triethylamine (0.346 mL, 2.497 mmol) and methanesulfonyl chloride (0.146 mL, 1.872 mmol). It was stirred at roomtemperature for 12 hours. After the end of the reaction, the mixture waspoured into 0.1M hydrochloric acid and extracted with ethyl acetate. Theorganic layer was washed with saturated aqueous sodium bicarbonate andbrine, respectively and dried over magnesium sulfate. The solvent wasevaporated under reduced pressure. Compound 38 (452 mg, 1.140 mmol, 91%)was obtained.

Compound 38; ¹H-NMR (CDCl₃) δ: 2.88 (s, 3H), 3.01 (s, 6H), 7.42-7.50 (m,3H), 7.60-7.61 (m, 2H), 7.87 (s, 1H), 7.95 (s, 1H).

To a solution of Compound 38 (452 mg, 1.140 mmol) in THF (4 mL) and theMeOH (2 mL) was added at room temperature 2M aqueous sodium hydroxide.It was stirred for 2 hours. The reaction mixture was concentrated underreduced pressure. The obtained residue was diluted with water, acidifiedwith 10% aqueous citric acid and extracted with ethyl acetate. Theorganic layer was washed with brine and dried over magnesium sulfate.The solvent was evaporated under reduced pressure. The obtained residuewas purified with silicagel chromatography (n-hexane:ethyl acetate) togive Compound 39 (290 mg, 0.911 mmol, 80%).

Compound 39; ¹H-NMR (CDCl₃) δ: 2.86 (s, 3H), 2.93 (s, 3H), 6.50 (br s,1H), 7.36-7.38 (m, 2H), 7.46-7.54 (m, 3H), 7.70 (s, 1H), 8.23 (s, 1H).

Example 11

To a solution of Compound 31 (2.36 g, 14.37 mmol) in 2-propanol (35 mL)was added at room temperature under nitrogen atmosphere N-chlorosuccinimide (2.111 g, 15.81 mmol). It stirred for 20 minutes at 65° C.After the end of the reaction, it was cooled to room temperature. Thereaction mixture was poured into saturated aqueous sodium bicarbonateand extracted twice with dichloromethane. The organic layer was washedwith brine and dried over sodium sulfate. The solvent was evaporatedunder reduced pressure. The obtained residue was purified with silicagelchromatography (n-hexane:ethyl acetate) to give Compound 40 (1.73 g, 8,71 mmol, 61%) as a thin orange solid.

Compound 40; ¹H-NMR (CDCl₃) δ: 2.84 (s, 3H), 4.18 (d, J=1.0 Hz, 2H),6.85 (d, J=8.6 Hz, 1H), 7.47 (d, J=8.1 Hz, 1H).

To a solution of Compound 40 (1.72 g, 8.66 mmol) in 2-propanol (35 mL)was added at room temperature under nitrogen atmosphere N-bromosuccinimide (1.695 g, 9.52 mmol). It was stirred for 15 minutes at 65°C. After the end of the reaction, the mixture was cooled to roomtemperature and poured into saturated aqueous sodium bicarbonate. Themixture was extracted twice with chloroform. The organic layer waswashed with brine and dried over magnesium sulfate. The solvent wasevaporated under reduced pressure. The obtained residue was purifiedwith silicagel chromatography (n-hexane:ethyl acetate) to give Compound41 (1.93 g, 6.95 mmol, 80%) as a thin yellow solid.

Compound 41; ¹H-NMR (CDCl₃) δ: 2.77 (s, 3H), 4.55 (br s, 2H), 7.94 (s,1H).

To a solution of Compound 41 (0.96 g, 3.46 mmol) in 1,4-dioxane (10 mL)and water (2.0 mL) were added at room temperature under nitrogenatmosphere phenyl boronic acid (0.633 g, 5.19 mmol),tetrakis(triphenylphosphine)palladium (0) (0.400 g, 0.346 mmol) andsodium carbonate (0.916 g, 8.65 mmol). It was stirred for 20 minutes at140° C. under microwave irradiation. After the end of the reaction,ethyl acetate was added to the reaction mixture. The organic layer wasconcentrated under reduced pressure. It was purified with silicagelchromatography (n-hexane ethyl acetate) to give Compound 42 (1.44 g,5.24 mmol, 76%) as a yellows solid.

Compound 42; ¹H-NMR (DMSO-d₆) δ: 2.78 (s, 3H), 4.88 (br s, 2H),7.42-7.53 (m, 5H), 7.63 (s, 1H).

To a solution of isoamyl nitrite (0.515 mL, 3.82 mmol) in acetonitrile(14 mL) was added under ice-cooling and nitrogen atmosphere CuCl₂ (428mg, 3.18 mmol). To the solution was gradually added Compound 42 (700 mg,2.55 mmol). It was stirred under ice-cooling for 20 minutes.Furthermore, it was stirred at 50° C. for 2 hours. The reaction mixturewas poured into 0.1M HCl aqueous solution and extracted with ethylacetate. The organic layer was washed with saturated aqueous sodiumbicarbonate and brine, respectively and dried over magnesium sulfate.The solvent was evaporated under reduced pressure. The obtained residuewas purified with silicagel chromatography (n-hexane:ethyl acetate) togive Compound 43 (636 mg, 2.162 mmol, 85%) as a white solid.

Compound 43; ¹H-NMR (CDCl₃) δ: 2.93 (s, 3H), 7.43-7.51 (m, 5H), 7.71 (s,1H).

Example 12

To a solution of Compound 42 (683 mg, 2.486 mmol) in formic acid (14 mL)was added at room temperature 35% formaldehyde solution (1.956 mL, 24.86mmol). It was heated for 1 hour under reflux. The reaction mixture wascooled to room temperature and was made basic by slowly adding saturatedaqueous sodium bicarbonate. The mixture was extracted with ethylacetate. The organic layer was washed with water and brine, respectivelyand dried over magnesium sulfate. The solvent was evaporated underreduced pressure. The residue was purified with silicagel chromatography(n-hexane:ethyl acetate) to give Compound 44 (213 mg, 0.703 mmol, 28.3%)as a solid.

Compound 44; ¹H-NMR (CDCl₃) δ: 2.68 (s, 6H), 2.88 (s, 3H), and 7.35-7.44(m, 5H) and 7.56 (s, 1H).

Example 13

To a solution of isoamyl nitrite (0.416 mL, 2.96 mmol) in acetonitrile(11 mL) was added under ice-cooling and nitrogen atmosphere CuBr (340mg, 2.371 mmol). After that, Compound 42 (543 mg, 1.976 mmol) was addedlittle by little to the solution. It was stirred under ice-cooling for20 minutes. Furthermore, it was stirred at 50° C. for 2 hours. Thereaction mixture was poured into 0.1M HCl aqueous solution and extractedwith ethyl acetate. The organic layer was washed with saturated aqueoussodium bicarbonate and brine, respectively and dried over magnesiumsulfate. The solvent was evaporated under reduced pressure. The residuewas purified with silicagel chromatography (n-hexane:ethyl acetate) togive Compound 45 (325 mg, 0.960 mmol, 49%) as a solid.

Compound 45; ¹H-NMR (DMSO-d₆) δ: 2.87 (s, 3H) and 7.41-7.51 (m, 5H) and8.07 (s, 1H).

To a solution of Compound 45 (120 mg, 0.354 mmol) in 1,4-dioxane (1.4mL) and water (0.35 mL) were added at room temperature under nitrogenatmosphere tetrakis(triphenylphosphine)palladium(0) (20.47 mg, 0.018mmol), phenyl boron acid (51.8 mg, 0.425 mmol) and sodium bicarbonate(74.4 mg, 0.886 mmol). It was stirred for 40 minutes at 130° C. undermicrowave irradiation. The reaction mixture was poured into water andextracted with ethyl acetate. The organic layer was washed with brineand dried over sodium sulfate. The solvent was evaporated under reducedpressure. The residue was purified with silicagel chromatography(n-hexane ethyl acetate) to give Compound 46 (107 mg, 0.319 mmol, 90%).

Compound 46; ¹H-NMR (CDCl₃) δ: 2.93 (s, 3H), 7.06-7.28 (m, 10H), 7.77(s, 1H).

Example 14

To a solution of 2-methylbenzo[d]thiazol-6-amine 27 (1 g, 6.09 mmol) intoluene (10 mL) and t-BuOH (2 mL) were added at room temperature undernitrogen atmosphere bromobenzene (1.004 g, 6.39 mmol), palladium acetate(0.068 g, 0.304 mmol), X-Phos (0.290 g, 0.609 mmol) and sodiumtert-butoxide (0.819 g, 8.52 mmol). It was stirred for 30 minutes at150° C. under microwave irradiation. The reaction mixture was pouredinto water and extracted with ethyl acetate. The organic layer waswashed with saturated aqueous sodium bicarbonate and brine, respectivelyand dried over sodium sulfate. The solvent was evaporated under reducedpressure. The residue was purified with silicagel chromatography(n-hexane:ethyl acetate) to give Compound 47 (1.29 g, 5.37 mmol, 88%) asa solid.

Compound 47; ¹H-NMR (CDCl₃) δ: 2.81 (s, 3H), 5.83 (br s, 1H), 6.97-7.01(m, 1H), 7.10-7.17 (m, 3H), 7.29-7.34 (m, 2H), 7.53 (d, J=2.4 Hz, 1H),7.83 (d, J=8.6 Hz, 1H).

To a solution of compound 47 (450 mg, 1.872 mmol) in THF (45 mL) wasdropped at −60° C. under nitrogen atmosphere LHMDS (6.18 mL, 6.18 mmol).It was stirred for 30 minutes at −60° C. To the solution was added at−60° C. diethyl carbonate (0.347 mL, 4.12 mmol). The mixture was stirredat 0° C. for 1 hour. The reaction mixture was poured into 0.1Mhydrochloric acid and extracted with ethyl acetate. The organic layerwas washed with saturated aqueous sodium bicarbonate and brine,respectively and dried over sodium sulfate. The solvent was evaporatedunder reduced pressure. The residue was purified with silicagelchromatography (n-hexane:ethyl acetate) to give Compound 48 (503 mg,1.411 mmol, 75%) as a brown liquid.

Compound 48; ¹H-NMR (CDCl₃) δ: 3.77 (s, 3H), 3.78 (s, 3H), 4.16 (s, 2H),7.22-7.27 (m, 3H), 7.33-7.37 (m, 3H), 7.79 (d, J=2.0 Hz, 1H), 7.94 (d,J=8.6 Hz, 1H).

Example 15

To a solution of 5-bromo-2-methylbenzothiazole 6 (300 mg, 1.315 mmol) intoluene (3.0 mL) and t-BuOH (0.6 mL) were added at room temperatureunder nitrogen atmosphere piperidine (224 mg, 2.63 mmol), palladiumacetate (14.76 mg, 0.066 mmol), X-Phos (62.7 mg, 0.132 mmol) and sodiumtert-butoxide (177 mg, 1.841 mmol). It was stirred for 20 minutes at150° C. under microwave irradiation. The reaction mixture was pouredinto water and extracted with ethyl acetate. The organic layer waswashed with brine and dried over magnesium sulfate. The solvent wasevaporated under reduced pressure. The residue was purified withsilicagel chromatography (n-hexane:ethyl acetate) to give Compound 49(211 mg, 0.908 mmol, 69%).

Compound 49; ¹H-NMR (CDCl₃) δ: 1.60-1.65 (m, 2H), 1.74-1.80 (m, 4H),3.22 (t, J=5.6 Hz, 4H), 7.09 (dd, J=8.9, 2.3 Hz, 1H), 7.48 (d, J=2.5 Hz,1H), 7.65 (t, J=4.6 Hz, 1H).

Example 16

To a solution of 5-bromo-2-methylbenzothiazole 6 (1.2 g, 5.26 mmol) intoluene (10 mL) and t-BuOH (2 mL) were added at room temperature undernitrogen atmosphere N-methylaniline (620 mg, 5.79 mmol), palladiumacetate (59.1 mg, 0.263 mmol), X-Phos (251 mg, 0.526 mmol) and sodiumtert-butoxide (708 mg, 7.36 mmol). It was stirred for 20 minutes at 150°C. under microwave irradiation. The reaction mixture was poured intowater and extracted with ethyl acetate. The organic layer was washedwith brine and dried over magnesium sulfate. The solvent was evaporatedunder reduced pressure. The residue was purified with silicagelchromatography (n-hexane:ethyl acetate) to give Compound 50 (820 mg,3.22 mmol, 61%).

Compound 50; ¹H-NMR (CDCl₃) δ: 2.81 (s, 3H), 3.37 (s, 3H) 6.97 (t, J=7.4Hz, 1H), 7.59 (d, J=2.0 Hz, 1H) 7.04-7.07 (m, 3H), 7.27-7.30 (m, 2H),7.63 (d, J=8.6 Hz, 1H).

Example 17

In a mixed solvent of toluene (10 mL) and t-BuOH (2 mL) were suspendedunder nitrogen atmosphere 5-bromo-2-methylbenzothiazole 6 (1.2 g, 5.26mmol), N-propyl aniline 51 (0.782 g, 5.79 mmol), Pd(OAc)₂ (0.059 g,0.263 mmol), X-phos (0.251 g, 0.526 mmol) and t-BuONa (0.708 g, 7.36mmol). The obtained mixture was stirred at 150° C. for 30 minutes undermicrowave irradiation. To the reaction mixture were added Pd(OAc)₂(0.059 g, 0.263 mmol) and X-phos (0.251 g, 0.526 mmol). It was stirredat 150° C. for 30 minutes under microwave irradiation. The reactionmixture was filtered with celite. Water and ethyl acetate were added.The mixture was extracted. The organic layer was washed with brine anddried over magnesium sulfate. The solvent was evaporated under reducedpressure. The residue was purified with column chromatography to giveCompound 52 (1.29 g, 4.57 mmol).

Compound 52; ¹H-NMR (CDCl₃) δ: 0.96 (t, J=7.6 Hz, 3H), 1.69-1.77 (m, 2H)and 2.82 (s, 3H), 3.72 (t, J=7.6 Hz, 2H), 6.96 (t, J=7.4 Hz, 1H), 7.02(d, J=8.6 Hz, 3H), 7.25-7.29 (m, 2H), 7.58 (d, J=2.0 Hz, 1H), 7.62 (d,J=8.6 Hz, 1H).

Example 18

To a mixed solvent of toluene (9.2 mL) and t-BuOH (2.2 mL) were addedunder nitrogen atmosphere 6-bromo-2-methylbenzothiazole 53 (900 mg, 3.95mmol), Pd(OAc)₂ (44.3 mg, 0.197 mmol), X-phos (188 mg, 0.395 mmol) andt-BuONa (531 mg, 5.52 mmol). To the obtained mixture was addedN-methylaniline (0.470 ml, 4.34 mmol). It was stirred for 150° C. or 20minutes under microwave irradiation. To the reaction mixture were addedwater and ethyl acetate. The mixture was extracted. The organic layerwas washed with brine and dried over magnesium sulfate. The solvent wasevaporated under reduced pressure. The residue was purified with columnchromatography to give Compound 54 (868 mg, 3.41 mmol).

Compound 54; ¹H-NMR (CDCl₃) δ: 2.82 (s, 3H), 3.38 (s, 3H) 6.97-7.08 (m,3H), 7.15 (dd, J=8.9, 2.4 Hz, 1H), 7.27-7.35 (m, 2H), 7.44 (d, J=2.4 Hz,1H), 7.83 (d, J=8.9 Hz, 1H)

Example 19

In dioxane (10 mL) were suspended under nitrogen atmosphere6-bromo-2-methylbenzothiazole 53 (700 mg, 3.07 mmol), Pd₂(dba)₃ (141 mg,0.153 mmol) and Xantphos (178 mg, 0.307 mmol). To the obtained mixturewas added thiophenol sodium salt (487 mg, 3.68 mmol). It was stirred at130° C. for 15 minutes under microwave irradiation. To the reactionmixture were added 0.1N hydrochloric acid and ethyl acetate. Afterextraction, the organic layer washed with saturated sodium bicarbonateaqueous solution and brine, respectively and dried over magnesiumsulfate. The solvent was evaporated under reduced pressure. The residuewas purified with column chromatography to give Compound 55 (587 mg,2.28 mmol).

Compound 55; ¹H-NMR (CDCl₃) δ: 2.85 (s, 3H), 7.24-7.39 (m, 5H), 7.46(dd, J=8.6, 1.8 Hz, 1H), 7.83 (dd, J=1.8, 0.5 Hz, 1H), 7.89 (d, J=8.6Hz, 1H).

To a solution of Compound 55 (586.6 mg, 2.279 mmol) in dichloromethane(12 mL) was added at 0° C. mCPBA (1452 mg, 5.47 mmol). It was stirred at0° C. for 1 hour. To the reaction mixture was added saturated aqueoussodium bicarbonate and ethyl acetate. After extraction, the organiclayer was washed 10% aqueous sodium thiosulfate and brine, respectivelyand dried over magnesium sulfate. The solvent was evaporated underreduced pressure. The residue was purified by crystallization to giveCompound 56 (259 mg, 0.894 mmol).

Compound 56; ¹H-NMR (CDCl₃) δ: 2.90 (s, 3H), 7.49-7.62 (m, 3H),7.96-8.07 (m, 4H), 8.52 (dd, J=1.8, 0.6 Hz, 1H).

Example 20

To a solution of 5-amino-2-methylbenzothiazole 31 (3 g, 18.27 mmol) in2-propanol (30 mL) was added NCS (2.56 g, 19.18 mmol). It was stirred atroom temperature for 1.5 hours. Water and ethyl acetate were added tothe reaction mixture. After extraction, the organic layer was washedwith brine and dried over magnesium sulfate. The solvent was evaporatedunder reduced pressure. The residue was purified with columnchromatography to give Compound 57 (1.90 g, 9.56 mmol).

Compound 57; ¹H-NMR (CDCl₃) δ: 2.86 (s, 3H), 4.20 (br s, 2H), 6.86 (d,J=8.6 Hz, 1H), 7.49 (d, J=8.6 Hz, 1H).

To a suspension of Compound 57 (1.90 g, 9.56 mmol) concentratedhydrochloric acid (10 mL) was dropped at 0° C. a solution of sodiumnitrites (726 mg, 10.52 mmol) in H₂O (10 ml). It was stirred for 30minutes at the same temperature. Potassium iodide (23.8 g, 143 mmol)aqueous solution (50 ml) was dropped to the reaction mixture at 0° C. Itwas stirred at the same temperature for 1 hour. The reaction mixture wasneutralized with saturated aqueous sodium bicarbonate and extracted withchloroform. The organic layer was washed with 10% aqueous sodiumthiosulfate and brine, respectively and dried over magnesium sulfate.The solvent was evaporated under reduced pressure. The residue waspurified by crystallization to give Compound 58 (1.48 g, 4.79 mmol).

Compound 58; ¹H-NMR (CDCl₃) δ: 2.91 (s, 3H), 7.48 (d, J=8.4 Hz, 1H),7.81 (d, J=8.4 Hz, 1H).

In a mixed solvent of dioxane (8 mL) and H₂O (2 mL) were suspended undernitrogen atmosphere Compound 58 (799 mg, 2.58 mmol), 4-fluoro benzeneboronic acid (542 mg, 3.87 mmol), tetrakis(triphenylphosphine) palladium(298 mg, 0.258 mmol) and sodium bicarbonate (542 mg, 6.45 mmol). Theobtained mixture was stirred at 120° C. for 1 hour under microwaveirradiation. To the reaction mixture were added water and ethyl acetate.After extraction, the organic layer was washed with saturated aqueoussodium bicarbonate and brine, respectively and dried over magnesiumsulfate. The solvent was evaporated under reduced pressure. The residuewas purified with column chromatography to give Compound 59 (464 mg,1.67 mmol).

Compound 59; ¹H-NMR (CDCl₃) δ: 2.93 (s, 3H), 7.14-7.21 (m, 2H), 7.34 (d,J=8.2 Hz, 1H), 7.45-7.52 (m, 2H), 7.77 (d, J=8.2 Hz, 1H).

Example 21

In a mixed solvent of THF (200 mL) and NMP (20 mL) were dissolved6-bromo-2-chlorobenzothiazole 1 (15 g, 60.4 mmol) and Fe(acac)₃ (1.07 g,3.02 mmol). To the obtained mixture was added at 0° C. 3M methylmagnesium bromide ethereal solution (24.14 ml, 72.4 mmol). It wasstirred at room temperature for 1.5 hours. To the reaction mixture wasadded at 0° C. 3M methyl magnesium bromide ethereal solution (10.1 ml,30.2 mmol). It was stirred at room temperatures for 1 hour. To thereaction mixture 1N aqueous hydrochloric acid and ethyl acetate. Afterextraction, the organic layer was washed with brine and dried overmagnesium sulfate. The solvent was evaporated under reduced pressure.The residue was purified with column chromatography to give Compound 53(10.6 g, 46.5 mmol).

Compound 53; ¹H-NMR (CDCl₃) δ: 2.82 (s, 3H), 7.54 (dd, J=8.7, 2.0 Hz,1H), 7.80 (d, J=8.7 Hz, 1H), 7.95 (d, J=2.0 Hz, 1H).

Example 22

To a solution of 4-bromo-2-chloroaniline 60 (2.50 g, 12.11 mmol) inacetic acid (25 ml) was added at room temperature potassium thiocyanate(4.71 g, 48.4 mmol). To the mixture was dropped for 15 minutes asolutions of bromine (1.25 ml, 24.22 mmol) in acetic acid (5 ml). Afterthe end of dropping, it was stirred at room temperature for 15 minutesand further stirred at 30° C. for 1 hour. After the end of the reaction,the mixture was neutralized with aqueous sodium hydroxide underice-cooling and extracted with ethyl acetate. The organic layer waswashed with saturated sodium bicarbonate solution and brine,respectively and dried over sodium sulfate. The solvent was evaporatedunder reduced pressure. To the residue was added ethyl acetate anddi-isopropyl ether. The mixture was filtered to give Compound 61 (2.02g, yield 43.3%) as a yellow solid.

Compound 61; ¹H-NMR (DMSO-d₆) δ: 7.48 (dd, J=2.1, 0.9 Hz, 1H), 7.89 (dd,J=2.7, 1.8 Hz, 1H), 7.97 (brs, 2H).

To a suspension of copper chloride (II) (1.78 g, 13.20 mmol) inacetonitrile (29 ml) was added under ice-cooling and nitrogen atmosphereisopentyl nitrate (2.22 ml, 16.51 mmol). To the mixture was added for 10minutes 2-amino-6-bromo-4-chlorobenzo[d]thiazole 61 (2.90 g, 11.00mmol). It was stirred at room temperature for 10 minutes. The mixturewas heated at 60° C. for 2 hours. After the end of the reaction, 2N HClwas added to the mixture. The mixture was extracted with ethyl acetate.The organic layer was washed with water and brine, respectively anddried over sodium sulfates. The solvent was evaporated under reducedpressure. The residue was purified with column chromatography(n-hexane:ethyl acetate=4:1) to give Compound 62 (1.60 g, yield 51.4%).

Compound 62; ¹H-NMR (DMSO-d₆) δ: 7.93 (d, J=1.8 Hz, 1H), 8.40 (d, J=1.8Hz, 1H).

Example 23

To a solution of 4-bromo-2-fluoroaniline 63 (5.0 g, 26.30 mmol) inacetic acid (50 ml) was added at room temperature potassium thiocyanate(10.23 g, 105.00 mmol). To the solution was dropped at room temperaturefor 15 minutes bromine (2.71 ml, 52.60 mmol) in acetic acid (12 ml).After the end of dropping, it was stirred at room temperature for 2hours. After the end of the reaction, the mixture was neutralized withaqueous sodium hydroxide under ice-cooling and extracted with ethylacetate. The organic layer was washed with saturated sodium bicarbonatesolution and saturated NaCl solution and dried over sodium sulfate. Thesolvent was evaporated under reduced pressure. The obtained residue waspurified with column chromatography (chloroform:methanol=20:1) to giveCompound 64 (3.67 g, yield 56.1%) as a yellow solid.

Compound 64; ¹H-NMR (DMSO-d₆) δ: 7.35 (dd, J=10.5, 1.8 Hz, 1H), 7.77 (d,J=2.1 Hz, 1H), 7.84 (brs, 2H).

To a suspension of copper chloride (II) (645 mg, 4.80 mmol) in mixedsolvent of acetonitrile (10 ml) and N-methyl-2-pyrrolidone (2 ml) wasadded under nitrogen atmosphere and ice-cooling isopentyl nitrate (0.81ml, 6.00 mmol). To the suspension was added for 10 minutes2-amino-6-bromo-4-fluorobenzo[d]thiazole 64 (988 mg, 4.00 mmol). It wasstirred at room temperature for 10 minutes and then heated at 60° C. for1 hour. After the end of the reaction, 2N HCl was added to the mixture.The mixture was extracted with ethyl acetate. The organic layer waswashed with water and brine, respectively and dried over sodium sulfate.The solvent was evaporated under reduced pressure. The obtained residuewas purified with column chromatography (chloroform) to give Compound 65(3.67 g, yield 56.1%) as a yellow solid.

Compound 65; ¹H-NMR (DMSO-d₆) δ: 7.78 (dd, J=10.2, 1.8 Hz, 1H), 8.27(dd, J=1.5, 0.6 Hz, 1H).

Example 24

To a solution of 2-amino-3,5-dibromopyridine 66 (5.0 g, 19.85 mmol) inacetone (50 ml) was dropped under ice-cooling benzoyl isothiocyanate(3.83 ml, 28.5 mmol). It was stirred at room temperature for 18 hours.The precipitate solid was collected by filtration and washed withhexane. The obtained product was dried under reduced pressure to giveCompound 67 (7.30 g, yield 83.0%) as a white solid.

Compound 67; ¹H-NMR (DMSO-d₆) δ: 7.56 (t, J=7.8 Hz, 2H), 7.68 (t, J=5.7Hz, 1H) 8.00 (d, J=7.5 Hz, 2H), 8.59 (d, J=1.5 Hz, 1H), 8.67 (d, J=2.1Hz, 1H), 11.89 (s, 1H), 12.38 (s, 1H).

To a suspension of N-(3,5-dibromopyridin-2-ylcarbamothiyl)benzamide 67(7.30 g, 17.59 mmol) in methanol (8 ml) was added 2N NaOH aqueoussolution (70.3 ml, 175 mmol). It was heated under reflux for 1 hour.After the end of the reaction, the mixture was cooled to roomtemperature. The precipitate was collected by filtration and washed withwater. The obtained product was dried under reduced pressure to giveCompound 68 (5.10 g, yield 93%) as a white solid.

Compound 68; ¹H-NMR (DMSO-d₆) δ: 8.43 (d, J=2.4 Hz, 1H), 8.52 (d, J=2.1Hz, 1H), 8.61 (brs, 1H), 9.32 (brs, 1H), 9.69 (brs, 1H).

To a solution of 60% sodium hydride (2.03 g, 50.80 mmol) indimethylformamide (75 ml) was added under ice-cooling for 15 minutes1-(3,5-dibromopyridin-2-yl)thiourea 68 (5.10 g, 16.40 mmol). It wasstirred for 15 minutes at room temperature and stirred for 3 hours at80° C. After the end of the reaction, it was cooled. To the mixture wereadded saturated NH₄Cl and water. It was stirred for 30 minutes. Theprecipitate was collected by filtration and washed with water. Theobtained product was dried under reduced pressure to give Compound 69(3.0 g, yield 80%) as a yellow solid.

Compound 69; ¹H-NMR (DMSO-d₆) δ: 8.11 (brs, 2H), 8.28 (dd, J=2.4, 0.9Hz, 1H), 8.32 (dd, J=2.4, 0.9 Hz, 1H).

To a suspension of copper chloride (II) (2.10 g, 15.65 mmol) inN-methyl-2-pyrrolidone (30 ml) was added under nitrogen atmosphere andice-cooling isopentyl nitrate (2.63 ml, 19.56 mmol). To the mixture wasadded for 10 minutes 6-bromothiazolo[4,5-b]pyridine-2-amine 69 (3.00 g,13.04 mmol). It was stirred for 10 minutes at room temperature. Then itwas stirred at 60° C. for 1 hour. After the end of the reaction, 2N HClwas added to the mixture. The mixture was extracted with ethyl acetate.The organic layer was washed with water and brine, respectively anddried over sodium sulfate. The solvent was evaporated under reducedpressure. The obtained residue was purified with column chromatography(chloroform:methanol=30:1) to give Compound 70 (1.50 g, yield 46.1%) asa yellow solid.

Compound 70; 1 H-NMR (DMSO-d₆) δ: 8.81 (d, J=2.4 Hz, 1H), 8.90 (d, J=2.4Hz, 1H).

To a solution of 2M NaHMDS THF solution (0.464 ml, 0.882 mmol) inanhydrous toluene (2.5 ml) was dropped under nitrogen atmosphere at −60°C. for 10 minutes ethyl acetate (0.043 ml, 0.88 mmol). Then it wasstirred at −60° C. for 1 hour. To the mixture was dropped a solution of6-bromo-2-chlorothiazolo[4,5-b]pyridine 70 (100 mg, 0.401 mmol) inanhydrous THF (8 ml) and toluene (2.5 ml). After dropping, it wasstirred at 0° C. for 2 hours.

To the reaction mixture was added saturated NH₄Cl aqueous solution andethyl acetate. After extraction, the organic layer was washed with brineand dried over magnesium sulfate. The solvent was evaporated underreduced pressure. The obtained residue was purified with columnchromatography (chloroform:methanol=20:1) to give the mixture ofCompounds 71 and 71′ as a yellow solid (107 mg, yield 89.0%).

Compound 71:71′(mix); ¹H-NMR (DMSO-d₆) δ: 1.19 (t, J=6.3 Hz, 2H), 1.24(t, J=6.3 Hz, 3H) 4.07 (q, J=6.8 Hz, 2H), 4.18 (q, J=6.8 Hz, 2H) 4.42(s, 2H), 5.41 (s, 1H) 8.21 (d, J=2.1 Hz, 1H), 8.25 (d, J=2.1 Hz, 1H),8.77 (d, J=2.1 Hz, 1H), 8.93 (d, J=2.1 Hz, 1H) 12.42 (brs, 1H).

Example 25

To a solution of 2-amino-3,5-dibromopyrazine 72 (497 mg, 1.96 mmol) inacetone (50 ml) was added isothianic acid ethyl ester (2.31 ml, 19.6mmol). It was stirred for 10 minutes at 100° C. under reflux. To themixture was added methanol (8 ml). It was stirred for 30 minutes at 80°C. It was cooled under ice-cooling. The precipitate was collected byfiltration and washed with water:methanol (2:1). The obtained productwas dried under reduced pressure to give Compound 73 (mg 487, yield82.0%) as a brown solid.

Compound 73; ¹H-NMR (DMSO-d₆) δ: 1.30 (t, J=7.2 Hz, 3H), 4.30 (q, J=1.2Hz, 2H), 8.72 (d, J=1.2 Hz, 1H), 12.75 (brs, 1H).

To a suspension of ethyl 6-bromothiazolo[4,5-b]pyrazin-2-ylcarbamate 73(480 mg, 1.58 mmol) in methanol (8 ml) was added 2N sodium hydroxideaqueous solution (7.91 ml, 15.83 mmol). It was heated for 5 hours underreflux. After the end of the reaction, the mixture was acidified with 2NHCl. Then the mixture was neutralized with saturated sodium bicarbonateand extracted with ethyl acetate. The organic layer was washed withsaturated sodium bicarbonate solution and saturated NaCl aqueoussolution and dried over sodium sulfate. The solvent was evaporated underreduced pressure. The precipitate was collected by filtration to giveCompound 74 (334 mg, yield 91.0%) as a white yellow solid.

Compound 74; ¹H-NMR (DMSO-d₆) δ: 8.37 (s, 1H), 8.59 (brs, 2H).

To a suspension of copper chloride (II) (2.17 g, 16.20 mmol) inN-methyl-2-pyrrolidone (30 ml) was added under nitrogen atmosphere andice-cooling isopentyl nitrate (2.73 ml, 20.25 mmol). Then2-amino-6-bromothiazolo[4,5-b]pyrazine 74 (3.12 g, 13.50 mmol) was addedfor 10 minutes to the mixture. It was stirred at room temperature for 10minutes and further stirred at 60° C. for 1 hour. After the end of thereaction, 2N HCl was added to the mixture. The mixture was extractedwith ethyl acetate. The organic layer was washed with water and brine,respectively and dried over sodium sulfate. The solvent was evaporatedunder reduced pressure. The obtained residue was purified with columnchromatography (chloroform) to give Compound 75 (3.67 g, yield 56.1%) asa yellow solid.

Compound 75; ¹H-NMR (DMSO-d₆) δ: 8.99 (d, J=0.9 Hz, 1H).

To a solution of 2M NaHMDS THF solution (3.700 ml, 7.03 mmol) inanhydrous toluene (8.0 ml) was dropped at −60° C. for 10 minutes undernitrogen atmosphere ethyl acetate (0.34 ml, 3.51 mmol). Then it wasstirred at −60° C. for 1 hour. To the mixture was dropped a solution of6-bromo-2-chlorothiazolo[4,5-b]pyrazine 75 (800 mg, 3.19 mmol) inanhydrous THF (8 ml) and toluene (8.0 ml). After dropping, it wasstirred at −60° C. for 1 hour.

To the reaction mixture was added saturated NH₄Cl aqueous solution andethyl acetate. After extraction, the organic layer was washed with brineand dried over magnesium sulfate. The solvent was evaporated underreduced pressure. The obtained residue was purified with columnchromatography (chloroform:methanol=20:1) to give the mixture ofCompounds 76 and 76′ as a yellow solid (650 mg, yield 67.4%).

Compound 76, 76′(mix); ¹H-NMR (DMSO-d₆) δ: 1.21 (t, J=6.4 Hz, 3H), 1.24(t, J=6.4 Hz, 3H) 4.11 (q, J=6.4 Hz, 2H), 4.20 (q, J=6.4 Hz, 2H), 4.48(s, 2H), 5.25 (s, 1H), 8.25 (s, 1H), 8.94 (s, 1H), 12.75 (brs, 1H).

Example 26

To a solution of Compound 77 (300 mg, 1.45 mmol) in acetic acid (20 ml)was added at room temperature potassium thiocyanate (565 mg, 5.81 mmol).To the mixture was slowly dropped under ice-cooling bromine (0.112 mL,2.18 mmol) in acetic acid (4 ml). After dropping, the mixture wasstirred at room temperature for 3 hours. After the end of the reaction,the mixture was neutralized under ice-cooling with aqueous sodiumhydroxide and then extracted ethyl acetate. The organic layer was washedwith saturated sodium bicarbonate aqueous solution and saturated NaClaqueous solution and dried over sodium sulfate. The solvent wasevaporated under reduced pressure. The obtained residue was purifiedwith column chromatography (n-hexane:ethyl acetate=1:1) to give themixture of Compounds 78 and 79 (79:79=1:1) as a white solid (190 mg).

Compound 78; ¹H-NMR (DMSO-d₆) δ: 7.22 (d, J=8.11 Hz, 1H), 7.52 (s, 1H),7.55 (d, J=8.11 Hz, 1H), 7.81 (s, 2H), 7.86 (s, 2H), 8.09 (s, 1H).

Example 27

To a solution of Compound 80 (5 g, 24.8 mmol) in acetone (150 mL) wasadded under ice-cooling benzoyl isothiocyanate (3.83 mL, 28.5 mmol). Itwas stirred under ice-cooling for 60 minutes. The precipitate solid wascollected by filtration and washed with diethyl ether. The obtainedproduct was dried under reduced pressure to give Compound 81 (8.1 g,90%) as a white solid.

Compound 81; ¹H-NMR (DMSO-d₆) δ: 3.86 (s, 3H), 7.27 (m, 1H), 7.52-7.70(m, 5H), 7.98 (d, J=8.11 Hz, 2H), 11.64 (s, 1H), 12.64 (s, 1H).

To a suspension of Compound 81 (8 g, 21.9 mmol) in methanol (80 ml) wasadded 2N NaOH aqueous solution (88 mL, 175 mmol). It was heated underreflux for 2 hours. After the end of the reaction, it was cooled to roomtemperature. MeOH was evaporated under reduced pressure. The precipitatesolid was collected by filtration and washed with water. The obtainedproduct was dried under reduced pressure to give Compound 82 (5.3 g,93%) as a white solid.

Compound 82; ¹H-NMR (DMSO-d₆) δ: 3.82 (s, 3H), 6.90 (dd, J=8.62, 2.03Hz, 1H), 7.36 (d, J=2.03 Hz, 1H), 7.47 (d, J=8.62 Hz, 1H), 9.77 (s, 1H).

To a suspension of Compound 82 (5 g, 19.15 mmol) in acetic acid (75 ml)was slowly dropped under ice-cooling bromine (0.987 mL, 19.15 mmol) inacetic acid (75 mL). After dropping, it was stirred at room temperaturefor 1 hour. Then it was heated at 50° C. for further 1 hour. After theend of the reaction, the mixture was neutralized under ice-cooling withsodium hydroxide aqueous solution and extracted with ethyl acetate. Theorganic layer was washed with saturated sodium bicarbonate aqueoussolution and saturated NaCl aqueous solution and dried over sodiumsulfate. The solvent was evaporated under reduced pressure. The obtainedresidue was suspended in ethyl acetate (50 mL). The suspension stirredfor 1 hour. The precipitate solid was collected by filtration to giveCompound 83 (4.73 g, 95%) as a white solid.

Compound 83; ¹H-NMR (DMSO-d₆) δ: 3.83 (s, 3H), 7.06 (s, 1H), 7.56 (brs,2H), 7.83 (s, 1H).

Example 28

A solution of Compound 34 (350 mg, 1.46 mmol) in concentratedhydrochloric acid (2 mL) was diluted with water (2 mL). To the solutionwas dropped under ice-cooling an aqueous solution (2 mL) of sodiumnitrite (111 mg, 1.60 mmol). It was stirred for 30 minutes. To themixture was slowly dropped an aqueous solution (10 mL) of potassiumiodide (3.63 g, 21.85 mmol). It was stirred at room temperature for 1hour. The reaction mixture was neutralized under ice-cooling with sodiumhydroxide solution and then extracted with chloroform. The organic layerwas washed with 10% aqueous solution of sodium thiosulfate and brine,respectively and dried over magnesium sulfate. The solvent wasevaporated under reduced pressure. The residue was purified with silicagel column chromatography (n-hexane:ethyl acetate=4:1) to give Compound84 (360 mg, 70%) as a white solid.

Compound 84; ¹H-NMR (DMSO-d₆) δ: 2.82 (s, 3H), 7.34-7.50 (m, 5H), 8.03(s, 1H), 8.49 (s, 1H).

To a suspension of copper iodide (I) (191 mg, 1.00 mmol) in DMF (1.5 mL)was added 2,2-difluoro-2-(fluorosulfonyl)methyl acetate (0.403 mL, 3, 19mmol). To the mixture was dropped a DMF solution (3 mL) of Compound 84(320 mg, 0.911 mmol). It was stirred at 120° C. for 1 hour. The mixturewas quenched with saturated aqueous ammonium chloride and extracted withethyl acetate. The organic layer was washed with water and brine,respectively. The solvent was evaporated under reduced pressure. Theresidue was purified with silica gel column chromatography(n-hexane:ethyl acetate=4:1) to give Compound 85 (180 mg, 67%) as awhite solid.

Compound 85; ¹H-NMR (DMSO-d₆) δ: 2.87 (s, 3H), 7.35-7.40 (m, 2H),7.43-7.48 (m, 3H), 8.13 (s, 1H), 8.32 (s, 1H).

Example 29

To a solution of Compound 86 (8.2 g, 40.6 mmol) in acetone (250 ml) wasadded benzoyl isothiocyanate (6.27 mL, 46.7 mmol). It was stirred underice-cooling for 60 minutes. The precipitate solid was collected byfiltration and washed with diethyl ether. The obtained product was driedunder reduced pressure to give Compound 87 (12.7 g, 86%) as a whitesolid.

Compound 87; ¹H-NMR (DMSO-d₆) δ: 3.88 (s, 3H), 7.16 (d, J=8.62 Hz, 1H),7.52-7.58 (m, 3H), 7.67 (m, 1H), 7.96-8.00 (m, 3H), 11.58 (s, 1H), 12.43(s, 1H).

To a suspension of Compound 87 (12.7 g, 34.8 mmol) in methanol (120 ml)was added 2N NaOH aqueous solution (139 mL, 278 mmol). It was heated for2 hours under reflux. After the end of the reaction, it was cooled toroom temperature. MeOH was evaporated under reduced pressure. Theprecipitate solid was collected by filtration and washed with water. Theobtained product was dried under reduced pressure to give Compound 88(8.72 g, 96%) as a white solid.

Compound 88; ¹H-NMR (DMSO-d₆) δ: 3.82 (s, 3H), 7.07 (d, J=9.12 Hz, 1H),7.27 (dd, J=9.12, 2.03 Hz, 1H), 7.64 (d, J=2.03 Hz, 1H), 9.54 (s, 1H).

To a suspension of Compound 88 (3 g, 11.49 mmol) in acetic acid (60 mL)was slowly dropped under ice-cooling an acetic acid solution (12 ml) ofbromine (0.651 mL, 12.64 mmol). After dropping, the mixture was heatedto 50 C and stirred for 4 hours. After the end of the reaction, themixture was neutralized under ice-cooling with sodium hydroxide aqueoussolution and extracted with ethyl acetate. The organic layer was washedwith saturated sodium bicarbonate aqueous solution and saturated NaClaqueous solution and dried over sodium sulfate. The solvent wasevaporated under reduced pressure. The obtained residue was suspended inethyl acetate (30 mL). The suspension stirred for 1 hour. Theprecipitate solid was collected by filtration to give Compound 89 (2.18g, 73%) as a white solid.

Compound 89; ¹H-NMR (DMSO-d₆) δ: 3.81 (s, 3H), 7.41 (brs, 2H), 7.50 (s,1H), 7.51 (s, 1H).

Example 30

To 1M LHMDS/THF solution (18.5 mL, 18.5 mmol) was slowly dropped at −60°C. a solution of Compound 90 (1.5 g, 8.42 mmol) in THF (15 ml). It wasstirred for 30 minutes. To the reaction mixture was added diethylcarbonate (1.23 mL, 10.11 mmol). It was stirred at 0° C. for 4 hours.After the end of the reaction, the reaction mixture was quenched withsaturated aqueous ammonium chloride aqueous solution and extracted withethyl acetate. The organic layer was washed with brine and dried overmagnesium sulfate. The solvent was evaporated under reduced pressure.The residue was purified with silica gel column chromatography(n-hexane:ethyl acetate=4:1) to give Compound 91 (900 mg, 43%) as ayellow oil.

Compound 91; LC/MS/Rt=1.86 min, MS:251.85 (M+1), method:C

To a solution of Compound 91 (900 mg, 3.60 mmol) in THF (9.0 ml) andEtOH (4.5 ml) was added 2N NaOH aqueous solution (2.0 mL, 3.96 mmol). Itwas stirred at room temperature for 2 hours. After the end of thereaction, the solvent was evaporated under reduced pressure. Theobtained residue was dissolved in DMF (9.0 mL). To the solution wereadded one by one H-Gly-OtBu hydrochloride salt (905 mg, 5.40 mmol), HATU(2.1 g, 5.40 mmol) and Pyridine (0.871 mL, 10.80 mmol). It was stirredat room temperature for 3 hours. After the end of the reaction, themixture was quenched with 10% aqueous citric acid and extracted withethyl acetate. The organic layer was washed with saturated sodiumbicarbonate aqueous solution and saturated sodium chloride aqueoussolution and dried over magnesium sulfate. The solvent was evaporatedunder reduced pressure. The residue was purified with silica gel columnchromatography (n-hexane:ethyl acetate=1:1) to give Compound 92 (264 mg,22%) as a yellow oil.

Compound 92; LC/MS/Rt=1.81 min, MS:336.95 (M+1), method:C

To a solution of Compound 92 (230 mg, 0.686 mmol) in dioxane (3 mL) wereadded (E)-styryl boronic acid (152 mg, 1.029 mmol), Pd(PPh₃)₄ (55.5 mg,0.048 mmol) and 3M K₂CO₃ aq. (0.686 mL, 12.058 mmol). It was stirred at120° C. for 25 minutes under microwave irradiation. After the end of thereaction, the insoluble was removed by celite filtration. The obtainedsolution was extracted with ethyl acetate. The organic layer was washedwith water and brine, respectively and dried over magnesium sulfate. Thesolvent was evaporated under reduced pressure. The residue was purifiedwith silica gel column chromatography (n-hexane:ethyl acetate=1:1) togive Compound 93 (70 mg, 29%) as a yellow oil. Compound 93; ¹H-NMR(CDCl₃) δ: 1.47 (s, 9H), 3.96-3.99 (m, 4H), 6.86 (d, J=16.22 Hz, 1H),7.16 (d, J=16.22 Hz, 1H), 7.28-7.40 (m, 3H), 7.44-7.50 (m, 3H), 7.68 (s,1H).

The compounds shown below were prepared in accordance with the aboveexample. The data of NMR or LC/MS were shown for each compounds.

TABLE 1 retention No. Structure NMR( δ) time Mass method II-1-5

1H-NMR (DMSO-d6) δ: 4.16 (s, 2H), 4.41 (d, J = 6.1 Hz, 2H), 7.38-7.56(m, 5H), 7.72-7.78 (m, 3H), 7.84 (d, J = 7.6 Hz, 1H), 7.91 (s, 1H), 8.14(d, J = 8.1 Hz, 1H), 8.21 (d, J = 1.0 Hz, 1H), 8.94 (t, J = 5.8 Hz, 1H),12.95 (br s, 1H). II-1-6

1H-NMR (DMSO-d6) δ: 4.14 (s, 2H), 4.40 (d, J = 5.6 Hz, 2H), 7.46 (t, J =7.6 Hz, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.64 (dd, J = 8.6, 2.0 Hz, 1H),7.83 (d, J = 7.6 Hz, 1H), 7.88-7.90 (m, 2H), 8.36 (d, J = 2.0 Hz, 1H),8.94 (t, J = 5.8 Hz, 1H), 12.93 (br s, 1H). II-1-7

1H-NMR (DMSO-d6) δ: 4.17 (s, 2H), 4.42 (d, J = 6.1 Hz, 2H), 7.47 (t, J =7.6 Hz, 1H), 7.56 (d, J = 7.6 Hz, 1H), 7.82-7.88 (m, 4H), 7.91 (s, 1H),7.99 (d, J = 8.1 Hz, 2H), 8.07 (d, J = 8.6 Hz, 1H), 8.49 (d, J = 2.0 Hz,1H), 8.95 (t, J = 5.8 Hz, 1H), 12.96 (br s, 1H). II-1-8

1H-NMR (DMSO-d6) δ: 3.99 (s, 2H), 4.40 (d, J = 5.6 Hz, 2H), 7.34-7.41(m, 2H), 7.47 (t, J = 7.6 Hz, 1H), 7.55 (d, J = 7.6 Hz, 1H), 7.68-7.73(m, 2H), 7.84 (d, J = 7.6 Hz, 1H), 7.92 (s, 1H), 8.91 (t, J = 5.8 Hz,1H), 12.97 (br s, 1H). II-1-9

1H-NMR (DMSO-d6) δ: 1.84 (s, 3H), 4.35 (d, J = 6.6 Hz, 2H), 7.19 (brs,1H), 7.39-7.42 (m, 2H), 7.46- 7.53 (m, 3H), 7.75-7.87 (m, 5H), 8.05 (d,J = 8.7 Hz, 1H), 8.38 (d, J = 1.5 Hz, 1H), 8.82 (t, J = 5.7 Hz, 1H),12.89 (brs, 1H).

TABLE 2 retention No. Structure NMR(δ) time Mass method II-1-10

1H-NMR (DMSO-d6) δ: 4.17(s, 2H), 4.42(d, J = 5.6 Hz, 2H), 7.46(t, J =7.6 Hz, 1H), 7.55(d, J = 7.6 Hz, 1H), 7.71-7.77(m, 2H), 7.82-7.91(m,3H), 8.04- 8.10(m, 3H), 8.51(s, 1H), 8.95(t, J = 5.8 Hz, 1H), 12.97(brs, 1H). II-1-11

1H-NMR (DMSOd6) δ: 4.16(s, 2H), 4.43(d, J = 5.5 Hz, 2H), 7.39(t, J = 7.6Hz, 3H), 7.51(m, 4H), 7.76 (m, 5H), 8.03(d, J = 8.4 Hz, 1H), 8.38(s,1H), 8.99(s, 1H). II-1-12

1H-NMR (DMSO-d6) δ: 1.72(s, 6H), 4.34(d, J = 5.1 Hz, 2H), 7.40-7.53(m,5H), 7.73- 7.87(m, 5H), 8.05(d, J = 8.4 Hz, 1H), 8.38- 8.42(m,2H), 12.89(brs, 1H). II-1-13

1H-NMR (DMSO-d6) δ: 4.16(s, 2H), 4.39(d, J = 5.9 Hz, 2H), 7.52-7.37(m,5H), 7.62(d, J = 7.4 Hz, 1H), 7.81-7.72(m, 4H), 8.02(d, J = 8.6 Hz, 1H),8.38(d, J = 1.5 Hz, 1H), 8.93(d, J = 5.9 Hz, 1H), 9.04(s, 1H), 11.21(s,1H). II-1-14

1H-NMR (DMSO-d6) δ: 4.21(s, 2H), 4.51(d, J = 5.7 Hz, 2H), 7.39-7.50(m,3H), 7.65(d, J = 5.4 Hz, 1H), 7.76-7.80(m, 3H), 8.04-8.07(m, 2H),8.39(s, 1H), 8.69(d, J = 5.5 Hz, 1H), 9.12(s, 1H).

TABLE 3 retention No. Structure NMR(δ) time Mass method II-1-15

1H-NMR (DMSO-d6) δ: 1.59-1.65(m, 2H), 1.72- 1.78(m, 2H), 2.18-2.24(m, 2H), 2.41-2.45(m, 2H), 4.10(s, 2H), 4.40(d, J = 5.6 Hz, 2H), 6.26(br s,1H), 7.46(t, J = 7.6 Hz, 1H), 7.53-7.57(m, 2H), 7.81- 7.90(m, 3H),8.05(s, 1H), 8.91(t, J = 5.6 Hz, 1H), 12.95(br s, 1H) II-1-16

1H-NMR (DMSO-d6) δ: 3.81(s, 3H), 4.14(s, 2H), 4.41(d, J = 6.1 Hz, 2H),7.05(d, J = 8.6 Hz, 2H), 7.46(t, J = 7.6 Hz, 1H), 7.55(d, J = 7.6 Hz,1H), 7.68-7.75(m, 3H), 7.83(d, J = 7.6 Hz, 1H), 7.91(s, 1H), 7.98(d, J =8.1 Hz, 1H), 8.31(d, J = 2.0 Hz, 1H), 8.93(t, J = 5.8 Hz, 1H), 12.97(brs, 1H). II-1-17

1H-NMR (DMSO-d6) δ: 2.85(br s, 3H), 2.95(br s, 3H), 4.15(s, 2H), 4.39(d,J = 6.1 Hz, 2H), 7.26-7.41 (m, 5H), 7.50(t, J = 7.6 Hz, 2H),7.75-7.81(m, 3H), 8.01(d, J = 8.1 Hz, 1H), 8.38(s, 1H), 8.91(t, J = 5.8Hz, 1H). II-1-18

1H-NMR (DMSO-d6) δ: 2.78(d, J = 4.6 Hz, 3H), 4.15(s, 2H), 4.39(d, J =5.6 Hz, 2H), 7.37-7.52(m, 5H), 7.69-7.81(m, 5H), 8.02(d, J = 8.1 Hz,1H), 8.38-8.42(m, 2H), 8.91(t, J = 5.8 Hz, 1H). II-1-19

1H-NMR (DMSO-d6) δ: 4.16(s, 2H), 4.40(br s, 2H), 7.36-7.52(m, 6H),7.75-7.83(m, 5H), 7.98(br s, 1H), 8.03(dd, J = 8.1, 3.5 Hz, 1H), 8.38(s,1H), 8.90(br s, 1H).

TABLE 4 retention meth- No. Structure NMR(δ) time Mass od II-1-20

1H-NMR (DMSO-d6) δ: 3.55(s, 2H), 4.31(s, 2H), 6.98(d, J = 7.6 Hz, 1H),7.27(t, J = 7.8 Hz, 1H), 7.38-7.55(m, 5H), 7.72- 7.81(m, 3H), 8.04(d, J= 8.6 Hz, 1H), 8.40(s, 1H), 10.46(s, 1H), 12.35(br s, 1H). II-1-21

1H-NMR (DMSO-d6) δ: 3.22(s, 3H), 3.49(s, 3H), 4.15(s, 2H), 4.40(d, J =5.4 Hz, 2H), 7.42-7.50(m, 7H), 7.76-7.80(m, 3H), 8.02(d, J = 8.6 Hz,1H), 8.38(s, 1H), 8.92-8.95(br m, 1H). II-1-22

1H-NMR (DMSO-d6) δ: 3.70(s, 3H), 4.16(s, 2H), 4.39(d, J = 5.7 Hz, 2H),7.40-7.49(m, 5H), 7.61(d, J = 7.1 Hz, 1H), 7.73-7.79 (m, 4H), 8.02(d, J= 8.6 Hz, 1H), 8.38(s, 1H), 8.90-8.93 (br m, 1H), 11.74(s, 1H). II-1-23

1H -NMR (DMSO-d6) δ: 4.29(s, 2H), 4.44(d, J = 6.0 Hz, 2H), 7.47(t, J =7.5 Hz, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.83(d, J = 7.8 Hz, 1H), 7.90(s,1H), 8.06(d, J = 8.4 Hz, 1H), 8.62(d, J = 8.4 Hz, 1H), 9.01(t, J = 5.7Hz, 1H), 12.97(brs, 1H) II-1-24

1H-NMR (DMSO-d6) δ: 2.38(d, J = 5.0 Hz, 3H), 4.16(s, 2H), 4.44(d, J =6.2 Hz, 2H), 7.39-7.81(m, 10H), 8.02(d, J = 8.7 Hz, 1H), 8.37(s, 1H),8.97-9.01 (br m, 1H).

TABLE 5 retention No. Structure NMR(δ) time Mass method II-1-25

1H-NMR (DMSO-d6) δ: 2.54(s, 6H), 4.16(s, 2H), 4.46(d, J = 5.9 Hz, 2H),7.39(t, J = 7.4 Hz, 1H), 7.50(t, J = 7.5 Hz, 2H), 7.63-7.67(m, 4H),7.76- 7.80(m, 3H), 8.02(d, J = 8.4 Hz, 1H), 8.38(s, 1H), 8.98-9.00(br m,1H). II-1-26

1H-NMR (CDCl3) δ: 1.55 (s, 9H), 3.97(s, 2H), 4.48 (d, J = 5.6 Hz, 2H),4.76(br s, 2H), 7.18(dd, J = 8.6, 2.0 Hz, 1H), 7.28-7.55(m, 4H),8.03-7.81(m, 3H). 1.84 400.30 (ES+) C II-1-27

1H-NMR (DMSO-d6) δ: 3.19(s, 3H), 4.17(s, 2H), 4.47(d, J = 6.1 Hz, 2H),7.39(t, J = 7.4 Hz, 1H), 7.50(t, J = 7.6 Hz, 2H), 7.61-7.68(m, 2H),7.74- 7.83(m, 4H), 7.88(s, 1H), 8.03(d, J = 8.6 Hz, 1H), 8.38(d, J = 1.5Hz, 1H), 9.00(t, J = 5.8 Hz, 1H). II-1-28

1H-NMR (DMSO-d6) δ: 4.17(s, 2H), 4.41(d, J = 6.1 Hz, 2H), 7.41-7.49(m,3H), 7.56(d, J = 7.6 Hz, 1H), 7.65(t, J = 7.9 Hz, 1H), 7.75(t, J = 7.6Hz, 1H), 7.82-7.88(m, 2H), 7.92(s, 1H), 8.00-8.02(m, 2H), 8.95(t, J =5.6 Hz, 1H), 12.97(br s, 1H). II-1-29

1H-NMR (DMSO-d6) δ: 4.14(s, 2H), 4.53(d, J = 5.7 Hz, 2H), 7.06(d, J =3.9 Hz, 1H), 7.39-7.81(m, 7H), 8.00-8.03(m, 1H), 8.39(s, 1H),9.06-9.09(br m, 1H).

TABLE 6 retention No. Structure NMR(δ) time Mass method II-1-30

1H-NMR (DMSO-d6) δ: 1.24-1.82(m, 10H), 2.60- 2.67(m, 1H), 4.09(s, 2H),4.39(d, J = 6.1 Hz, 2H), 7.35(dd, J = 8.4, 1.8 Hz, 1H), 7.45(t, J = 7.6Hz, 1H), 7.53(d, J = 7.6 Hz, 1H), 7.81-7.90(m, 4H), 8.90(t, J = 5.8 Hz,1H). II-1-31

1H-NMR (DMSO-d6) δ: 3.80(dd, J = 19.3, 5.6 Hz, 4H), 4.15(s, 2H),7.34-7.53 (m, 3H), 7.69-7.82(m, 3H), 8.01(d, J = 8.6 Hz, 1H), 8.28(s,1H), 8.38(d, J = 10.0 Hz, 1H), 8.67(s, 1H). 1.64 384.00 (ES+) C II-1-32

1H-NMR (CDCl3) δ: 3.74 (s, 3H), 4.08(dd, J = 7.4, 5.8 Hz, 4H), 4.15(s,2H), 6.79(s, 1H), 7.26(s, 2H), 7.34-7.52(m, 3H), 7.60- 7.76(m, 3H),7.87(s, 1H), 8.09-8.00(m, 2H). II-1-33

1H-NMR (DMSO-d6) δ: 4.20(s, 2H), 4.42(d, J = 6.0 Hz, 2H), 7.45-7.57(m,4H), 7.92(s, 1H), 8.15-8.18(m, 3H), 8.41(d, J = 8.4 Hz, 1H), 8.97(t, J =5.7 Hz, 1H), 12.99(brs, 1H). II-1-34

1H-NMR (CDCl3) δ: 4.13 (s, 2H), 4.53(s, J = 5.7 Hz, 2H), 7.25-7.49(m,9H), 7.61-7.65(m, 2H), 7.71(d, J = 1.8, 8.7 Hz, 2H), 8.01 (d, J = 8.4Hz, 1H), 8.06(s, 1H)

TABLE 7 reten- tion meth- No. Structure NMR(δ) time Mass od II-1-35

1H-NMR (CDCl3) δ: 2.91 (t, J = 7.1 Hz, 2H), 3.66- 3.72(m, 2H), 4.13(s,2H), 4.54(d, J = 6.1 Hz, 2H), 6.15(s, 1H), 7.21-7.49(m, 10H),7.56-7.72(m, 6H), 8.01(d, J = 8.1 Hz, 1H), 8.06(d, J = 1.5 Hz, 1H).II-1-36

1.93 421.42 (ES+) A II-1-37

1.61 446.45 (ES+) A II-1-38

2.07 429.45 (ES+) A II-1-39

1H-NMR (DMSO-d6) δ: 4.22(s, 2H), 4.42(d, J = 5.7 Hz, 2H), 7.34(dd, J =8.4 Hz, 1H), 7.83(d, J = 7.8 Hz, 1H), 7.92(s, 1H), 8.21(d, J = 8.4 Hz,1H), 8.46(d, J = 8.4 Hz, 1H), 8.69-8.76(m, 1H), 8.69-8.76(m, 1H), 8.98-9.01(m, 2H), 12.81(brs, 1H).

TABLE 8 reten- tion meth- No. Structure NMR(δ) time Mass od II-1-40

1H-NMR (DMSO-d6) δ: 4.189(s, 2H), 4.43(d, J = 6.9 Hz, 2H), 7.36(t, J =7.2 Hz, 2H), 7.56 (d, J = 7.8 Hz, 1H), 7.83(d, J = 7.8 Hz, 1H), 7.92(s,1H), 8.13 (d, J = 8.4 Hz, 1H), 8.22(d, J = 6.6 Hz, 1H), 6.23(d, J = 6.6Hz, 1H), 8.40(d, J = 8.4 Hz, 1H), 8.99(t, J = 6.0 Hz, 1H), 12.99 (brs,1H), (s, 2H), 8.37(d, J = 7.2 Hz, 1H), 12.53(s, 1H) II-1-41

1H-NMR (DMSO-d6) δ: 4.17(s, 2H), 4.42(d, J = 5.6 Hz, 2H), 7.47(dd, J =7.6, 8.1 Hz, 1H), 7.56(d, J = 7.6 Hz, 1H), 7.80-7.93 (m, 5H),8.00-8.08(m, 3H), 8.48(d, J = 1.5 Hz, 1H), 8.95(t, J = 5.6 Hz, 1H),12.99(brs, 2H). II-1-42

1H-NMR (DMSO-d6) δ: 3.32(s, 3H), 4.18(s, 2H), 4.42(d, J = 5.7 Hz, 2H),7.47(t, J = 7.5 Hz, 1H), 7.56(d, J = 6.6 Hz, 1H), 7.75-7.96(m, 5H),8.10(dd, J = 7.5, 15 Hz, 3H), 8.27(s, 1H), 8.53(s, 1H), 8.97(m, 1H).II-1-43

1H-NMR (DMSO-d6) δ: 4.15(s, 2H), 4.41(d, J = 5.6 Hz, 2H), 6.80(dd, J =2.0, 7.6 Hz, 1H), 7.08-7.18 (m, 2H), 7.28(dd, J = 7.6, 8.1 Hz, 1H),7.47(dd, J = 7.6, 8.1 Hz, 1H), 7.56(d, J = 7.6 Hz, 1H), 7.71(dd, J =2.0, 8.1 Hz, 1H), 7.84(d, J = 8.1 Hz, 1H), 7.91(s, 1H), 8.00(d, J = 8.6Hz, 1H), 8.30(d, J = 2.0 Hz, 1H), 8.94(t, J = 5.6 Hz, 1H), 9.57(brs,1H), 13.00(brs, 1H). II-1-44

1H-NMR (DMSO-d6) δ: 4.18(s, 2H), 4.41(d, J = 5.6 Hz, 2H), 7.46(t, J =7.6 Hz, 1H), 7.55(d, J = 7.6 Hz, 1H), 7.79-7.84(m, 3H), 7.90-7.94(m,2H), 8.08(d, J = 8.1 Hz, 1H), 8.57(d, J = 1.5 Hz, 1H), 8.67(d, J = 6.1Hz, 2H), 8.96(t, J = 5.8 Hz, 1H), 12.97(br s, 1H).

TABLE 9 reten- tion meth- No. Structure NMR(δ) time Mass od II-1-45

1H-NMR (DMSO-d6) δ: 4.16(s, 2H), 4.42(d, J = 6.1 Hz, 2H), 7.47(dd, J =7.6, 8.1 Hz, 1H), 7.56(d, J = 7.6 Hz, 1H), 7.64(dd, J = 7.6, 8.1 Hz,1H), 7.79-7.86 (m, 2H), 7.91(s, 1H), 7.96 (d, J = 7.6 Hz, 1H), 7.99-8.07(m, 2H), 8.27(m, 1H), 8.45(d, J = 1.5 Hz, 1H), 8.95(t, J = 6.1 Hz,1H), 13.03(brs, 2H). II-1-46

1H-NMR (DMSO-d6) δ: 1.88(d, J = 5.6 Hz, 3H), 4.10(s, 2H), 4.40(d, J =5.6 Hz, 2H), 6.40(dt, J = 16.9, 5.4 Hz, 1H), 6.53(d, J = 16.2 Hz, 1H),7.41-7.55 (m, 3H), 7.82-7.90(m, 3H), 8.02(s, 1H), 8.91(t, J = 5.6 Hz,1H), 12.95(br s, 1H). II-1-47

1H-NMR (DMSO-d6) δ: 4.17(s, 2H), 4.41(d, J = 6.1 Hz, 2H), 7.41-7.50(m,3H), 7.53-7.58(m, 1H), 7.77-7.88(m, 4H), 7.91(s, 1H), 8.04(d, J = 1.5Hz, 1H), 8.99(t, J = 6.1 Hz, 1H). II-1-48

1H-NMR (DMSO-d6) δ: 4.11(s, 2H), 4.42(d, J = 6.1 Hz, 2H), 7.60-7.38(m,3H), 7.94-7.67(m, 4H), 9.00(t, J = 5.8 Hz, 1H). II-1-49

1H-NMR (DMSO-d6) δ: 2.72(m, 2H), 7.35(m, 2H), 3.77(m, 2H), 4.14(s, 2H),4.40(d, J = 6.0 Hz, 2H) 6.31((s, 1H), 7.48(t, 7.5 Hz, 2H), 7.55(d, J =7.5 Hz, 1H), 7.82(d, J = 7.5 Hz, 2H), 7.92(-7.95 (m, 3H), 8.18(d, J =1.84 Hz, 1H) 8.99(t, J = 6.0 Hz, 1H), 9.29 (brs, 1H).

TABLE 10 reten- tion meth- No. Structure NMR(δ) time Mass od II-1-50

2.66 377.05 (+)ESI C II-1-51

1H-NMR (DMSO-d6) δ: 2.07(s, 3H), 4.14(s, 2H), 4.41(d, J = 5.6 Hz, 2H),7.46(dd, J = 7.6, 8.1 Hz, 1H), 7.52-7.58(m, 1H), 7.70(m, 4H), 7.76(dd, J= 1.5, 8.6 Hz, 1H), 7.80-7.86 (m, 1H), 7.91(s, 1H), 7.99 (d, J = 8.6 Hz,1H), 8.33(d, J = 1.5 Hz, 1H), 8.94(t, J = 5.6 Hz, 1H), 10.05(s, 1H),12.94(brs, 1H). II-1-52

1H-NMR (DMSO-d6) δ: 4.04(s, 2H), 7.25(s, 1H), 7.39-7.41(m, 1H), 7.50(t,J = 7.6 Hz, 2H), 7.76-7.79 (m, 4H), 8.01(d, J = 8.6 Hz, 1H), 8.38(d, J =1.8 Hz, 1H). II-1-53

1H-NMR (DMSO-d6) δ: 0.90(t, J = 7.1 Hz, 3H), 1.59-1.69(m, 2H), 2.68(t, J= 7.6 Hz, 2H), 4.09(s, 2H), 4.39(d, J = 6.1 Hz, 2H), 7.32(d, J = 8.6 Hz,1H), 7.45(t, J = 7.6 Hz, 1H), 7.53(d, J = 7.6 Hz, 1H), 7.81-7.90(m, 4H),8.91(t, J = 6.1 Hz, 1H). II-1-54

1H-NMR (DMSO-d6) δ: 3.14(s, 6H), 4.17(s, 2H), 4.41(d, J = 5.6 Hz, 2H),7.42-7.60(m, 5H), 7.80- 7.88(m, 2H), 7.91(s, 1H), 8.05(d, J = 8.6 Hz,1H), 8.43(d, J = 1.5 Hz), 8.99(t, J = 5.6 Hz, 1H).

TABLE 11 reten- tion meth- No. Structure NMR(δ) time Mass od II-1-55

1H-NMR (DMSO-d6) δ: 4.18(s, 2H), 4.42(d, J = 6.1 Hz, 2H), 7.36-7.42(m,1H), 7.47(dd, J = 7.6, 8.1 Hz, 1H), 7.52-7.65(m, 2H), 7.67-7.86(m, 4H),7.91 (brs, 1H), 8.07(d, J = 8.1 Hz, 1H), 8.38(d, J = 1.5 Hz, 1H),9.01(t, J = 6.1 Hz, 1H). II-1-56

1H-NMR (DMSO-d6) δ: 2.08(s, 3H), 4.16(s, 2H), 4.41(d, J = 5.6 Hz, 2H),7.34-7.50(m, 3H), 7.52- 7.61(m, 2H), 7.71(dd, J = 8.1, 2.0 Hz, 2H),7.81-7.86 (m, 1H), 7.91(s, 1H), 7.97 (s, 1H), 8.03(d, J = 8.6 Hz, 1H),8.30(d, J = 1.5 Hz, 1H), 8.95(t, J = 5.6 Hz, 1H), 10.05(s, 1H), 12.96(brs, 1H). II-1-57

1H-NMR (DMSO-d6) δ: 4.17(s, 2H), 4.42(d, J = 5.6 Hz, 2H), 7.47(dd, J =7.6, 8.1 Hz, 1H), 7.51-7.60 (m, 3H), 7.80-7.87(m, 1H), 7.89-7.99(m, 4H),8.00- 8.10(m, 3H), 8.33(s, 1H), 8.54(d, J = 1.5 Hz, 1H), 8.96(t, J = 5.6Hz, 1H), 12.97(brs, 1H). II-1-58

1H-NMR (DMSO-d6) δ: 0.89(t, J = 7.1 Hz, 3H), 4.02(q, J = 7.1 Hz, 2H),4.16(s, 2H), 4.42(d, J = 5.6 Hz, 2H), 7.37(dd, J = 1.8, 8.4 Hz, 1H),7.44-7.56 (m, 4H), 7.61-7.68(m, 1H), 7.76-7.86(m, 2H), 7.92(s, 1H),7.97(d, J = 8.4 Hz, 1H), 8.00(d, J = 1.5 Hz, 1H), 8.95(t, J = 5.6 Hz,1H), 12.96(brs, 1H). II-1-59

1H-NMR (DMSO-d6) δ: 1.40(d, J = 6.9 Hz, 3H), 4.12(s, 2H), 4.97(t, J =7.3 Hz, 1H), 7.24-7.25(m, 1H), 7.33-7.39(m, 5H), 7.50(t, J = 7.5 Hz,2H), 7.75-7.79 (m, 3H), 8.01(d, J = 8.6 Hz, 1H), 8.37(s, 1H), 8.84(d, J= 7.4 Hz, 1H).

TABLE 12 retention No. Structure NMR(δ) time Mass method II-1-60

1H-NMR (DMSO)-d6) δ: 4.19(s, 2H), 4.47(d, J = 6.0 Hz, 2H), 5.37(s, 2H),7.34-7.58(m, 9H), 7.75- 7.80(m, 3H), 8.02-8.04(m, 2H), 8.37(s, 1H),8.66(d, J = 5.2 Hz, 1H), 9.03-9.06(br m, 1H). II-1-61

1H-NMR (DMSO-d6) δ: 4.00(s, 2H), 4.37(d, J = 4.1 Hz, 2H), 7.39(t, J =7.4 Hz, 1H), 7.50(t, J = 7.6 Hz, 2H), 7.74-7.80(m, 3H), 8.00(d, J = 8.1Hz, 1H), 8.38(d, J = 1.5 Hz, 1H), 9.47(s, 1H). II-1-62

0.98 432.47 (ES+) A II-1-63

1.41 526.48 (ES+) A II-1-64

1H-NMR (DMSO-d6) δ: 4.16(s, 2H), 4.36(d, J = 5.2 Hz, 2H), 7.14-7.22(m,3H), 7.39-7.50(m, 4H), 7.76-7.80(m, 3H), 8.02(d, J = 8.4 Hz, 1H),8.39(s, 1H), 8.99(br s, 1H).

TABLE 13 reten- tion No. Structure NMR(δ) time Mass method II-1-65

1H-NMR (DMSO-d6) δ: 4.12(s, 3H), 4.38(d, J = 6.6 Hz, 2H), 7.44(t, J =7.8 Hz, 1H), 7.51-7.59(m, 3H), 7.78(dd, J = 8.1, 12 Hz, 2H), 7.88(s,1H), 7.94(d, J = 8.4 Hz, 1H). 8.36(s, 1H), 8.92(m, 1H) II-1-16

1H-NMR (DMSO-d6) δ: 2.01(s, 3H), 4.13(s, 2H), 4.30(d, J = 5.9 Hz, 2H),6.97(d, J = 7.2 Hz, 1H), 7.24(t, J = 8.3 Hz, 1H), 7.44(dd, J = 25.3, 6.6Hz, 5H), 7.76-7.79(m, 3H), 8.01(d, J = 8.6 Hz, 1H), 8.38(s, 1H),8.85-8.88(br m, 1H), 9.92(s, 1H). II-1-67

1H-NMR (CDCl3) δ: 1.57 (s, 9H), 4.11(s, 2H), 4.54 (d, J = 5.7 Hz, 2H),6.99(t, J = 9.0 Hz, 1H), 7.18(br-s, 1H), 7.35-7.41(m, 2H), 7.47(m, 1H),7.87-7.91(m, 2H). II-1-68

1H-NMR (CDCl3) δ: 2.26 (s, 6H), 2.51(t, J = 5.8 Hz, 2H), 3.51-3.52(m,2H), 4.14(s, 2H), 4.57(d, J = 5.6 Hz, 2H), 6.85(s, 1H), 7.37-7.49(m,5H), 7.62- 7.76(m, 6H), 8.02(d, J = 8.6 Hz, 1H), 8.06(d, J = 1.5 Hz,1H). II-1-69

1H-NMR (DMSO-d6) δ: 1.16(d, J = 6.6 Hz, 6H), 4.02-4.15(m, 3H), 4.39(d, J= 5.6 Hz, 2H), 7.37-7.52 (m, 5H), 7.70-7.81(m, 5H), 8.02(d, J = 8.6 Hz,1H), 8.19(d, J = 8.1 Hz, 1H), 8.38(d, J = 1.5 Hz, 1H), 8.90(t, J = 5.8Hz, 1H).

TABLE 14 reten- tion meth- No. Structure NMR(δ) time Mass od II-1-70

1H-NMR (DMSO-d6) δ: 2.19(s, 6H), 2.36(t, J = 6.6 Hz, 2H), 3.22-3.23(m,2H), 4.07(s, 2H), 7.39(t, J = 7.4 Hz, 1H), 7.50(t, J = 7.6 Hz, 2H),7.74-7.80(m, 3H), 8.00(d, J = 8.1 Hz, 1H), 8.33(br s, 1H), 8.38(d, J =1.5 Hz, 1H). II-1-71

1H-NMR (CDCl3) δ: 2.66 (br s, 1H), 3.59-3.63(m, 2H), 3.82-3.83(m, 2H),4.14(s, 2H), 4.55(d, J = 6.1 Hz, 2H), 6.69(br s, 1H), 7.36-7.49(m, 5H),7.62- 7.75(m, 6H), 8.01(d, J = 8.1 Hz, 1H), 8.06(d, J = 1.5 Hz, 1H).II-1-72

1H-NMR (DMSO-d6) δ: 4.15(s, 2H), 4.34(d, J = 5.7 Hz, 2H), 7.22(d, J =5.1 Hz, 2H), 7.39(t, J = 7.2 Hz, 1H), 7.49(d, J = 7.8 Hz, 2H), 7.74-7.83(m, 5H), 8.02(d, J = 8.4 Hz, 1H), 8.38(d, J = 1.5 Hz, 1H), 8.93(d, J =6.3 Hz, 1H). II-1-73

1H-NMR (DMSO)-d6) δ: 4.18(s, 2H), 4.41(d, J = 5.4 Hz, 2H), 7.40-7.57(m,3H), 7.82-7.89(m, 3H), 8.96(m, 1H), 12.86(br-s, 1H) II-1-74

1.76 445.47 (ES+) A

TABLE 15 retention No. Structure NMR(δ) time Mass method II-1-75

2.19 459.44 (ES+) A II-1-76

1.96 421.48 (ES+) A II-1-77

2.06 417.5 (ES+) A II-1-78

1.86 409.39 (ES+) A II-1-79

2.15 459.44 (ES+) A

TABLE 16 NMR retention No. Structure (δ) time Mass method II-1-80

2.22 487.47 (ES+) A II-1-81

2.25 495.51 (ES+) A II-1-82

1.56 496.45 (ES+) A II-1-83

1.72 393.41 (ES+) A II-1-84

1.26 454.43 (ES+) A

TABLE 17 NMR retention No. Structure (δ) time Mass method II-1-85

2.07 449.46 (ES+) A II-1-86

2.66 473.53 (ES+) A II-1-87

1.22 393.45 (ES+) A II-1-88

2.04 393.44 (ES+) A II-1-89

1.26 405.42 (ES+) A

TABLE 18 NMR retention No. Structure (δ) time Mass method II-1-90

1.29 404.2 (ES+) A II-1-91

2 417.41 (ES+) A II-1-92

2.02 525.38 (ES+) A II-1-93

1.48 433.44 (ES+) A II-1-94

1.88 447.41 (ES+) A

TABLE 19 NMR retention No. Structure (δ) time Mass method II-1-95

2.03 462.45 (ES+) A II-1-96

2.08 449.41 (ES+) A II-1-97

1.77 493.49 (ES+) A II-1-98

2.35 479.41 (ES+) A II-1-99

2.14 435.49 (ES+) A

TABLE 20 NMR retention No. Structure (δ) time Mass method II-1-100

1.76 463.44 (ES+) A II-1-101

2.15 435.41 (ES+) A II-1-102

2.07 439.4 (ES+) A II-1-103

2.25 431.45 (ES+) A II-1-104

1.91 451.48 (ES+) A

TABLE 21 NMR retention No. Structure (δ) time Mass method II-1-105

2.1 447.46 (ES+) A II-1-106

2.06 439.38 (ES+) A II-1-107

2.22 431.45 (ES+) A II-1-108

2.15 455.4 (ES+) A II-1-109

0.95 432.53 (ES+) A

TABLE 22 NMR retention No. Structure (δ) time Mass method II-1-110

2.3 527.5 (ES+) A II-1-111

2.35 479.43 (ES+) A II-1-112

1.64 436.41 (ES+) A II-1-113

1.87 403.32 (ES+) A II-1-114

1.99 389.34 (ES+) A

TABLE 23 NMR retention No. Structure (δ) time Mass method II-1-115

1.63 341.29 (ES+) A II-1-116

(DMSO-d6) δ: 2.89 (1H, s), 3.16 (2H, s), 4.07 (1H, s), 4.26 (1H, s),4.32 (1H, s), 4.42 (1H, s) 7.40 (1H, d, J = 7.1 Hz), 7.50 (2H, t, J =7.2 Hz), 7.78 (3H, t, J = 11.2 Hz), 8.01 (1H, t, J = 7.2 Hz), 8.39 (1H,s). II-1-117

(DMSO-d6) δ: 1.97 (2H, s), 3.71 (2H, d, J = 22.7 Hz), 4.20 (1H, s), 4.34(1H, ), 7.39 (1H, s), 7.50 s (2H, s), 7.77 (2H, t, J = 11.5 Hz), 8.01(1H, d, J = 7.8 Hz), 8.38 (1H, s), 8.66 (1H, s). II-1-118

2.13 267.25 (ES+) A II-1-119

(DMSO-d6) δ: 0.92 (6H, t, J = 5.1 Hz), 2.10 (1H, dd, J = 13.3, 7.2 Hz),4.20 (2H, d, J = 9.3 Hz), 4.24 (1H, d, J = 8.8 Hz), 7.39 (1H, t, J = 7.3Hz), 7.50 (2H, t, J = 7.6 Hz), 7.75 (2H, d, J = 7.6 Hz), 7.79 (1H, d, J= 8.6 Hz), 8.01 (1H, d, J = 8.6 Hz), 8.38 (1H, s), 8.59 (1H, d, J = 7.8Hz).

TABLE 24 NMR retention No. Structure (δ) time Mass method II-1-120

(DMSO-d6) δ: 1.95 (2H, dd, J = 12.5, 5.9 Hz), 2.19 (1H, t, J = 8.7 Hz),3.46 (2H, s), 3.69 (2H, dd, J = 12.5, 6.7 Hz), 4.31 (1H, d, J = 7.1 Hz),4.35 (1H, d, J = 6.3 Hz), 7.39 (1H, t, J = 7.1 Hz), 7.50 (2H, t, J = 7.3Hz), 7.77 (3H, t, J = 11.1 Hz), 8.01 (1H, t, J = 7.2 Hz), 8.38 (1H, s).II-1-121

(DMSO-d6) δ: 1.87 (1H, s), 2.05 (1H, s), 2.42 (2H, s), 3.59 (3H, s),4.14 (2H, s), 4.30 (1H, s), 7.40 (1H, d, J = 7.3 Hz), 7.49 (2H, d, J =6.8 Hz), 7.77 (3H, dd, J = 15.7, 7.6 Hz), 8.01 (1H, d, J = 9.1 Hz), 8.38(1H, s), 8.72 (1H, d, J = 7.1 Hz). II-1-122

(DMSO-d6) δ: 2.57 (4H, s), 3.19 (3H, s), 3.59 (7H, s), 4.37 (2H, s),7.39 (1H, s), 7.50 (2H, s), 7.75 (3H, s), 8.02 (1H, s), 8.38 (1H, s).II-1-123

(DMSO-d6) δ: 2.57 (4H, s), 3.19 (3H, s), 3.59 (7H, s), 4.37 (2H, s),7.39 (1H, s), 7.50 (2H, s), 7.75 (3H, s), 8.02 (1H, s), 8.38 (1H, s).II-1-124

(DMSO-d6) δ: 1.48 (2H, dt, J = 47.4, 10.2 Hz), 1.85 (2H, d, J = 11.4Hz), 2.01 (1H, s), 2.82 (1H, t, J = 12.9 Hz), 3.19 (1H, t, J = 13.8 Hz),3.97 (1H, d, J = 16.7 Hz), 4.25 (1H, d, J = 13.1 Hz), 4.36 (2H, s), 7.39(1H, s), 7.49 (2H, d, J = 7.8 Hz), 7.77 (3H, t, J = 11.2 Hz), 8.01 (1H,d, J = 8.6 Hz), 8.38 (1H, s).

TABLE 25 NMR retention No. Structure (δ) time Mass method II-1-125

(DMSO-d6) δ: 1.48 (2H, dt, J = 47.4, 10.2 Hz), 1.85 (2H, d, J = 11.4Hz), 2.01 (1H, s), 2.82 (1H, t, J = 12.9 Hz), 3.19 (1H, t, J = 13.8 Hz),3.97 (1H, d, J = 16.7 Hz), 4.25 (1H, d, J = 13.1 Hz), 4.36 (2H, s), 7.39(1H, s), 7.49 (2H, d, J = 7.8 Hz), 7.77 (3H, t, J = 11.2 Hz), 8.01 (1H,d, J = 8.6 Hz), 8.38 (1H, s). II-1-126

(DMSO-d6) δ: 4.37 (2H, s), 7.09 (1H, s). 7.39 (2H, s), 7.46 (2H, d, J =8.6 Hz), 7.49 (2H, d, J = 7.3 Hz), 7.68 (2H, d, J = 8.1 Hz), 7.76 (2H,d, J = 7.6 Hz), 7.81 (1H, d, J = 9.3 Hz), 8.05 (1H, d, J = 8.6 Hz), 8.42(1H, s), 11.78 (1H, s). II-1-127

(DMSO-d6) δ: 0.86 (1H, s), 1.99 (1H, s), 2.04 (2H, d, J = 8.3 Hz), 3.81(2H, t, J = 6.6 Hz), 4.13 (2H, s), 4.32 (2H, d, J = 5.6 Hz), 7.29 (2H,d, J = 7.1 Hz), 7.40 (1H, d, J = 8.8 Hz), 7.49 (2H, d, J = 6.1 Hz), 7.60(2H, d, J = 8.1 Hz), 7.73-7.81 (4H, m), 8.01 (1H, d, J = 8.3 Hz), 8.39(1H, s), 8.85 (1H, s). II-1-128

2.19 389.29 (ES+) A II-1-129

(DMSO-d6) δ: 1.38 (9H, s), 4.12 (2H, s), 4.14 (2H, s), 4.33 (2H, d, J =5.3 Hz), 5.75 (1H, s), 7.15 (3H, d, J = 11.6 Hz), 7.28 (1H, s), 7.39(2H, s), 7.49 (2H, d, J = 7.3 Hz), 7.77 (3H, dd, J = 15.8, 8.0 Hz), 8.02(1H, d, J = 7.8 Hz), 8.38 (1H, s), 8.88 (1H, s).

TABLE 26 NMR retention No. Structure (δ) time Mass method II-1-130

(DMSO-d6) δ: 4.12 (2H, s), 4.25 (2H, d, J = 5.8 Hz), 5.75 (1H, s), 5.98(2H, s), 6.78 (1H, d, J = 8.8 Hz), 6.86 (2H, d, J = 10.9 Hz), 7.40 (1H,s), 7.49 (2H, d, J = 7.6 Hz), 7.78 (3H, t, J = 12.4 Hz), 8.01 (1H, d, J= 7.8 Hz), 8.38 (1H, s), 8.80 (1H, s). II-1-131

2.16 403.31 (ES+) A II-1-132

(DMSO-d6) δ: 4.22 (2H, s), 4.54 (2H, d, J = 5.3 Hz), 7.41 (1H, d, J =6.8 Hz), 7.49 (3H, d, J = 6.8 Hz), 7.63 (1H, d, J = 7.1 Hz), 7.67 (1H,d, J = 7.8 Hz), 7.73 (3H, dd, J = 18.3, 8.7 Hz), 7.80 (1H, d, J = 8.6Hz), 8.04 (1H, d, J = 8.3 Hz), 8.39 (1H, s), 8.97 (1H, s). II-1-133

(DMSO-d6) δ: 4.18 (2H, s), 4.45 (2H, d, J = 5.8 Hz), 7.41 (1H, d, J =6.6 Hz), 7.52 (4H, dd, J = 17.4, 8.1 Hz), 7.71 (2H, d, J = 8.1 Hz), 7.76(2H, d, J = 1.1 Hz), 7.80 (1H, d, J = 8.1 Hz), 8.03 (1H, d, J = 8.3 Hz),8.39 (1H, s), 8.99 (1H, s). II-1-134

(DMSO-d6) δ: 4.18 (2H, s), 4.46 (2H, d, J = 5.8 Hz), 7.40 (1H, t, J =7.2 Hz), 7.50 (2H, t, J = 7.5 Hz), 7.61 (3H, d, J = 8.3 Hz), 7.67 (1H,s), 7.76 (2H, d, J = 7.8 Hz), 7.81 (1H, d, J = 8.6 Hz), 8.03 (1H, d, J =8.6 Hz), 8.39 (1H, s), 8.99 (1H, s).

TABLE 27 NMR retention No. Structure (δ) time Mass method II-1-135

(DMSO-d6) δ: 2.84 (3H, s), 3.61 (3H, s), 4.18 (2H, s), 4.43 (2H, d, J =29.8 Hz), 7.38 (2H, dd, J = 14.5, 5.7 Hz), 7.50 (2H, t, J = 7.7 Hz),7.58 (1H, d, J = 8.8 Hz), 7.71 (2H, d, J = 9.3 Hz), 7.75 (2H, d, J = 7.6Hz), 7.80 (1H, d, J = 10.6 Hz), 8.03 (1H, d, J = 8.3 Hz), 8.38 (1H, s),9.00 (1H, s). II-1-136

(DMSO-d6) δ: 2.84 (4H, s), 3.61 (4H, s), 4.18 (2H, s), 4.47 (2H, s),7.39 (1H, s), 7.49 (2H, d, J = 7.1 Hz), 7.59 (2H, d, J = 8.1 Hz), 7.71(2H, d, J = 8.8 Hz), 7.76 (2H, d, J = 8.3 Hz), 7.80 (1H, d, J = 8.6 Hz),8.03 (1H, d, J = 9.1 Hz), 8.39 (1H, s), 9.00 (1H, s). II-1-137

(DMSO-d6) δ: 4.22 (2H, s), 5.40 (1H, d, J = 6.8 Hz), 7.41 (7H, t, J =8.6 Hz), 7.49 (2H, d, J = 6.8 Hz), 7.75 (2H, d, J = 7.1 Hz), 7.99 (1H,s), 8.37 (1H, s), 9.18 (1H, s). II-1-138

(DMSO-d6) δ: 3.10 (1H, d, J = 7.8 Hz), 3.22 (1H, d, J = 9.1 Hz), 4.12(2H, d, J = 3.8 Hz), 4.56 (1H, d, J = 5.8 Hz), 6.96 (1H, t, J = 7.6 Hz),7.05 (1H, t, J = 7.3 Hz), 7.18 (1H, s), 7.33 (1H, d, J = 7.8 Hz), 7.39(1H, t, J = 7.5 Hz), 7.51 (3H, dd, J = 18.8, 7.7 Hz), 7.77 (3H, t, J =9.9 Hz), 8.00 (1H, d, J = 8.8 Hz), 8.35 (1H, s), 8.73 (1H, d, J = 8.1Hz), 10.87 (1H, s). II-1-139

(DMSO-d6) δ: 1.80 (1H, s), 1.99 (2H, s), 2.17 (2H, s), 4.14 (2H, s),4.23 (1H, s), 6.78 (1H, s), 7.31 (1H, s), 7.39 (1H, s), 7.49 (2H, d, J =6.8 Hz), 7.75 (3H, d, J = 7.8 Hz), 8.01 (1H, d, J = 7.8 Hz), 8.38 (1H,s), 8.72 (1H, s).

TABLE 28 NMR retention No. Structure (δ) time Mass method II-1-140

(DMSO-d6) δ: 2.59 (1H, s), 4.14 (2H, s), 4.56 (1H, s), 6.93 (1H, s),7.39 (2H, s), 7.49 (2H, d, J = 7.1 Hz), 7.77 (3H, t, J = 11.5 Hz), 8.01(1H, d, J = 8.3 Hz), 8.37 (1H, s), 8.67 (1H, s). II-1-141

(DMSO-d6) δ: 0.86 (3H, d, J = 6.1 Hz), 0.91 (3H, d, J = 6.6 Hz), 1.56(2H, s), 1.68 (1H, s), 4.14 (2H, s), 4.28 (1H, s), 7.40 (1H, d, J = 6.8Hz), 7.50 (2H, t, J = 7.8 Hz), 7.77 (3H, t, J = 11.4 Hz), 8.00 (1H, d, J= 8.1 Hz), 8.38 (1H, s), 8.68 (1H, d, J = 8.6 Hz). II-1-142

1.08 398.3 (ES+) A II-1-143

(DMSO-d6) δ: 1.90 (2H, s), 2.04 (3H, s), 4.15 (2H, s), 4.39 (2H, s),7.39 (1H, s), 7.49 (2H, d, J = 7.6 Hz), 7.74 (2H, s), 8.01 (1H, d, J =7.1 Hz), 8.38 (1H, s), 8.73 (1H, s). II-1-144

(DMSO-d6) δ: 2.92 (1H, t, J = 11.6 Hz), 3.11 (1H, t, J = 7.2 Hz), 4.09(2H, s), 4.50 (1H, d, J = 4.8 Hz), 7.19 (1H, s), 7.23 (4H, s), 7.40 (1H,d, J = 7.3 Hz), 7.50 (2H, t, J = 7.5 Hz), 7.77 (3H, t, J = 10.4 Hz),8.00 (1H, d, J = 8.3 Hz), 8.36 (1H, s), 8.75 (1H, d, J = 8.3 Hz).

TABLE 29 NMR retention No. Structure (δ) time Mass method II-1-145

(DMSO-d6) δ: 2.70 (2H, dd, J = 17.7, 6.1 Hz), 4.15 (2H, s), 4.60 (1H, d,J = 6.3 Hz), 7.40 (1H, d, J = 7.3 Hz), 7.50 (2H, t, J = 7.6 Hz), 7.77(3H, t, J = 11.7 Hz), 8.01 (1H, d, J = 8.3 Hz), 8.38 (1H, s), 8.79 (1H,d, J = 7.8 Hz). II-1-146

(DMSO-d6) δ: 1.40 (6H, s), 4.09 (2H, s), 7.40 (1H, d, J = 7.6 Hz) 7.50(2H, t, J = 7.3 Hz), 7.77 (3H, t, J = 10.9 Hz) 8.01 (1H, d, J = 8.6 Hz),8.38 (1H, s), 8.63 (1H, s). II-1-147

2.12 475.39 (ES+) A II-1-148

1.84 409.33 (ES+) A II-1-149

2.29 403.25 (ES+) A

TABLE 30 NMR retention No. Structure (δ) time Mass method II-1-150

1.54 417.31 (ES+) A II-1-151

1.75 353.28 (ES+) A II-1-152

2.38 423.51 (ES+) A II-1-153

1.27 461.39 (ES+) A II-1-154

2.05 401.29 (ES+) A

TABLE 31 retention No. Structure NMR(δ) time Mass method II-1-155

1.39 486.39 (ES+) A II-1-156

2.53 503.43 (ES+) A II-1-157

2.19 423.39 (ES+) A II-1-158

2.53 453.38 (ES+) A II-1-159

(DMSO-d6) δ: 352 (2H, s), 4.31 (2H, s), 7.22 (2H, d, J = 8.8 Hz), 7.40(1H, s), 7.50 (2H, s), 7.56 (2H, d, J = 8.1 Hz), 7.75 (3H, s), 8.03 (1H,s), 8.40 (1H, s), 10.45 (1H, s).

TABLE 32 retention No. Structure NMR(δ) time Mass method II-1-160

2.23 417.45 (ES+) A II-1-161

1.65 355.32 (ES+) A II-1-162

1.89 369.42 (ES+) A II-1-163

(DMSO-d6) δ: 2.82 (3H, s), 5.75 (1H, s), 7.40 (1H, d, J = 7.3 Hz), 7.49(2H, t, J = 7.5 Hz), 7.76 (3H, t, J = 10.1 Hz), 7.97 (1H, d, J = 8.6Hz), 8.35 (1H, s). II-1-164

(DMSO-d6) δ: 4.17 (2H, s), 4.42 (2H, d, J = 6.1 Hz), 7.32 (2H, s), 7.40(1H, d, J = 7.1 Hz), 7.50 (4H, t, J = 8.1 Hz), 7.78 (5H, dd, J = 16.5,8.7 Hz), 8.03 (1H, d, J = 8.3 Hz), 8.39 (1H, s), 8.97 (1H, s).

TABLE 33 retention No. Structure NMR(δ) time Mass method II-1-165

(DMSO-d6) δ: 2.54 (2H, s), 2.98 (6H, s), 4.28 (2H, d, J = 5.3 Hz), 5.75(1H, s), 7.04 (1H, s), 7.25 (2H, s), 7.40 (1H, d, J = 6.3 Hz), 7.50 (2H,t, J = 6.9 Hz), 7.75-7.82 (4H, m), 8.01 (1H, d, J = 8.3 Hz), 8.38 (1H,s), 8.80 (1H, s). II-1-166

(DMSO-d6) δ: 4.18 (2H, s), 4.42 (2H, d, J = 5.3 Hz), 7.40 (1H, t, J =7.1 Hz), 7.50 (2H, t, J = 7.6 Hz), 7.56 (1H, t, J = 7.8 Hz), 7.66 (1H,d, J = 7.1 Hz), 7.73-7.81 (5H, m), 8.04 (1H, d, J = 8.6 Hz), 8.39 (1H,s), 8.95 (1H, s). II-1-167

2.53 353.27 (ES+) A II-1-168

2.47 409.49 (ES+) A II-1-169

2.23 389.45 (ES+) A

TABLE 34 retention No. Structure NMR(δ) time Mass method II-1-170

2.47 360.25 (ES+) A II-1-171

1.26 442.39 (ES+) A II-1-172

2.3 365.38 (ES+) A II-1-173

2.07 348.38 (ES+) A II-1-174

2.31 371.28 (ES+) A

TABLE 35 retention No. Structure NMR(δ) time Mass method II-1-175

1.52 410.42 (ES+) A II-1-176

2.26 444.48 (ES+) A II-1-177

2.3 425.36 (ES+) A II-1-178

2.19 403.28 (ES+) A II-1-179

2.23 389.38 (ES+) A

TABLE 36 retention No. Structure NMR(δ) time Mass method II-1-180

1.51 371.38 (ES+) A II-1-181

1.78 383.25 (ES+) A II-1-182

1.63 355.29 (ES+) A II-1-183

1.19 396.38 (ES+) A II-1-184

2.41 467.59 (ES+) A

TABLE 37 retention No. Structure NMR(δ) time Mass method II-1-185

2.65 474.39 (ES+) A II-1-186

1.22 472.51 (ES+) A II-1-187

0.23 354.47 (ES+) A II-1-188

0.24 340.44 (ES+) A II-1-189

1.5 342.41 (ES+) A

TABLE 38 retention No. Structure NMR(δ) time Mass method II-1-190

1.67 356.43 (ES+) A II-1-191

1.5 342.41 (ES+) A II-1-192

1H-NMR (DMSO-d6) δ: 4.19 (s, 2H), 4.44 (d, J = 5.2 Hz, 2H), 7.36-7.52(m, 4H), 7.76-7.79 (m, 3H), 7.96 (s, 1H), 8.04 (d, J = 8.4 Hz, 1H), 8.38(s, 1H), 8.55 (d, J = 4.7 Hz, 1H), 9.05 (br s. 1H). II-1-193

1H-NMR (CDCl3) δ: 1.57 (s, 9H), 4.15 (s, 2H), 4.56 (d, J = 5.6 Hz, 2H),7.21- 7.42 (m, 2H), 7.47-7.54 (m, 1H), 7.64-7.69 (m, 1H), 7.75-7.94 (m,4H). II-1-194

1H-NMR (CDCl3) δ: 1.56 (s, 9H), 4.13 (s, 2H), 4.51 (s, 2H), 7.26-7.55(m, 6H), 7.62-7.64 (m, 2H), 7.74 (d, J = 7.6 Hz, 1H), 7.85-7.89 (m, 3H),8.27 (s, 1H). 2.79 459.15 (ES+) C

TABLE 39 retention No. Structure NMR(δ) time Mass method II-1-195

4.09 417.25 (ES+) D II-1-196

1H-NMR (DMSO-d6) δ: 4.19 (s, 2H), 4.41 (d, J = 5.6 Hz, 2H), 7.34 (t, J =7.9 Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H), 7.55-7.57 (m, 1H), 7.73-7.74 (m,1H), 7.83 (d, J = 7.6 Hz, 1H), 7.89 (s, 1H), 8.03-8.12 (m, 1H), 8.96 (t,J = 5.6 Hz, 1H), 12.94 (s, 1H). 1.76 407.00 (ES+) C II-1-197

1H-NMR (DMSO-d6) δ: 4.14 (s, 2H), 4.39 (d, J = 6.1 Hz, 2H), 7.40-7.58(m, 7H), 7.84 (dd, J = 21.0, 14.4 Hz, 4H), 8.07 (d, J = 8.1 Hz, 1H),8.90 (t, J = 5.8 Hz, 1H), 12.93 (s, 1H). 2.1 403.05 (ES+) C II-1-198

1H-NMR (DMSO-d6) δ: 3.94 (s, 3H), 4.10 (s, 2H), 7.02 (d, J = 8.1 Hz,1H), 7.35(t, J = 8.1 Hz, 1H), 7.46(t, J = 7.5 Hz, 1H), 7.57 (dd, J = 7.5Hz, 2H), 7.83 (d, J = 7.2 Hz, 1H), 7.89 (s, 1H), 8.92 (m, 1H), 12.94(br-s, 1H). II-1-199

1H-NMR (DMSO-d6) δ: 1.20 (s, 9H), 4.15 (s, 2H), 4.40 (d, J = 5.9 Hz,2H), 7.39-7.52 (m, 5H), 7.69- 7.76 (m, 5H), 8.02 (d, J = 8.6 Hz, 1H),8.37 (d, J = 1.7 Hz, 1H), 8.90-8.94 (br m, 1H), 10.93 (s, 1H).

TABLE 40 retention No. Structure NMR(δ) time Mass method II-1-200

1H-NMR (DMS0-d6) δ: 4.15 (s, 2H), 4.39 (d, J = 5.5 Hz, 2H), 4.50 (s,2H), 7.42-7.50 (m, 5H), 7.64 (d, J = 7.4 Hz, 1H), 7.76-7.79 (m, 4H),8.02 (d, J = 8.4 Hz, 1H), 8.38 (s, 1H), 8.91 (br s, 1H). II-1-201

1H-NMR (DMSO-d6) δ: 2.20 (s, 3H), 4.08 (s, 2H), 4.39 (d, J = 5.6 Hz,2H), 6.92 (d, J = 7.6 Hz, 1H), 7.10-7.13 (m, 2H), 7.23 (t, J = 7.1 Hz,1H) 7.34 (d, J = 7.1 Hz, 1H), 7.45 (t, J = 7.6 Hz, 1H), 7.54-7.54 (m,2H), 7.83 (d, J = 7.6 Hz, 1H), 7.90-7.92 (m, 2H), 8.89 (t, J = 5.8 Hz,1H), 12.95 (br s, 1H) II-1-202

1H-NMR (DMSO-d6) δ: 4.18 (s, 2H), 4.42 (d, J = 5.6 Hz, 2H), 7.47 (t, J =7.6 Hz, 1H), 7.56 (d, J = 7.6 Hz, 1H), 7.74-7.84 (m, 4H), 7.91 (s, 1H),8.07-8.11 (m, 2H), 8.18 (d, J = 8.1 Hz, 1H), 8.32 (d, J = 1.5 Hz, 1H),8.95 (t, J = 5.8 Hz, 1H), 12.95 (br s, 1H). II-1-203

1H-NMR (CDCl3) δ: 1.46 (s, 9H), 4.00 (d, J = 5.1 Hz, 2H), 4.12 (s, 2H),7.33-7.42 (m, 1H), 7.43-7.50 (m, 2H), 7.54-7.66 (m, 3H), 7.71 (dd, J =8.4, 1.8 Hz, 1H), 8.11- 8.02 (m, 2H). II-1-204

1H-NMR (DMSO-d6) δ: 1.54 (s, 9H), 4.18 (s, 2H), 4.62 (d, J = 5.5 Hz,2H), 7.42-7 49 (m, 6H), 7.76- 7.80 (m, 4H), 8.02 (d, J = 8.4 Hz, 1H),8.39 (s, 1H), 8.75 (br s, 1H).

TABLE 41 retention No. Structure NMR(δ) time Mass method II-1-205

1H-NMR (DMSO-d6) δ: 3.60 (s, 3H), 4.17 (s, 2H), 6.27-6.38 (m, 3H),7.03(t, J = 7.8 Hz, 1H), 7.50(t, J = 7.2 Hz, 1H), 7.75-7.90(m, 4H), 8.39(d, J = 1.8 Hz, 1H), 10.11 (s, 1H). II-1-206

1H-NMR (DMS0-d6) δ: 4.19 (s, 2H), 6.99 (d, J = 6.3, 2.4 Hz, 1H),737-7.41 (m, 2H), 7.50(t, J = 7.8 Hz, 2H), 7.52-7.82 (m, 3H), 8.06 (d, J= 8.7 Hz, 1H), 8.16 (d, J = 2.4 Hz, 1H), 8.39 (d, J = 2.4 Hz, 1H),10.23(d, J = 2.4 Hz, 1H), 12.78(brs, 1H). II-1-207

1H-NMR (DMSO-d6) δ: 4.18 (s, 2H), 6.68-6.80(m, 3H), 7.14(t, J = 7.2 Hz,2H), 7.41(t, J = 7.2 Hz, 1H), 7.53(t, J = 7.2 Hz, 2H), 7.81 (dd, J =8.4, 1.5 Hz, 1H),7.89(d, J = 2.4 Hz, 1H), 8.03(d, J = 1.8 Hz, 1H), 10.12(d, J = 2.7 Hz, 1H) II-1-208

1H-NMR (DMSO-d6) δ: 4.20(s, 2H), 694(dd, J = 8.1, 2.4 Hz, 1H), 7.17(d, J= 7.8 Hz, 1H), 7.24- 7.42(m, 3H), 7.75(d, J = 7.5 Hz, 2H), 7.81 (dd, J =7.2, 1.5 Hz, 1H)., 8.05(d, J = 8.4 Hz, 1H), 8.35(d, J = 1.8 Hz, 1H),8.39(d, J = 1.8 Hz, 1H), 10.17 (d, J = 2.1 Hz, 1H) II-1-209

1H-NMR (DMSO-d6) δ: 4.18 (s, 2H), 4.46 (d, J = 5.7 Hz, 2H), 7.39-7.42(m, 1H), 7.48-7.61 (m, 4H), 7.74-7.81 (m, 3H), 7.93 (d, J = 7.2 Hz, 1H),8.02 (d, J = 8.4 Hz, 2H), 8.38 (d, J = 1.5 Hz, 1H), 9.00 (br s, 1H).

TABLE 42 retention No. Structure NMR(δ) time Mass method II-1-210

1H-NMR (DMSO-d6) δ: 3.85 (s, 2H), 4.40 (d, J = 5.6 Hz, 2H), 7.93-7.28(m, 12H), 8.83 (t, J = 6.1 Hz, 1H). II-1-211

1H-NMR (DMSO-d6) δ: 4.19 (s, 2H), 4.69 (d, J = 5.7 Hz, 2H), 7.39-7.41(m, 2H), 7.47-7.55 (m, 4H), 7.74-7.82 (m, 3H), 7.89 (dd, J = 7.7, 1.2Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 8.38 (d, J = 1.5 Hz, 1H), 8.77 (br s,1H). II-1-212

1H-NMR (CDCl3) δ: 1.57 (s, 9H), 4.04 (s, 2H), 4.54 (d, J = 5.7 Hz, 2H),6.06 (s, 2H), 7.21 (s, 1H), 7.33-7.41 (m, 2H), 7.44-7.47 (m, 1H), 7.59(br-s, 1H), 7.87-7.90 (m, 2H) II-1-213

1H-NMR (DMSO-d6) δ: 4.04 (s, 2H), 4.39 (d, J = 6.0 Hz, 2H), 6.1 (s, 2H),7 46 (t, J = 8.4 Hz, 2H), 7.55 (t, J = 7.5 Hz, 2H), 7.83 (d, J = 7.5 Hz,1H), 7.89 (s, 1H), 8.89 (m, 1H), 12.96 (br-s, 1H). II-1-214

1H NMR (DMSO-d6) δ: 4.19 (s, 2H), 4.45 (d, J = 5.9 Hz, 2H), 7.26-7.52(m, 5H), 7.76-7.79 (m, 4H), 8.02 (d, J = 8.4 Hz, 1H), 8.39 (s, 1H), 8.52(d, J = 4.4 Hz, 1H), 8.97 (br s, 1H).

TABLE 43 retention No. Structure NMR(δ) time Mass method II-1-215

1H-NMR (DMSO-d6) δ: 4.19 (s, 2H), 4.36 (d, J = 5.9 Hz, 2H), 7.34-7.48(m, 5H), 7.76-7.80 (m, 3H), 8.03 (d, J = 8.6 Hz, 1H), 8.39 (s, 1H), 8.51(d, J = 5.5 Hz, 2H), 8.96 (br s, 1H). II-1-216

1H-NMR (DMSO-d6) δ: 1.43-1.68 (m, 6H), 1.78- 1.92 (m, 2H), 2.34-2.43 (m,1H), 3 71-3.82 (m, 1H), 4.06 (s, 2H), 7.34-7.53 (m, 3H), 7.70-7.81 (m,3H), 8.00 (d, J = 8.1 Hz, 1H), 8.40-8.26 (m, 2H). 3.69 394.95 (ES+) CII-1-217

1H NMR (DMSO-d6) δ: 4.18 (s, 2H), 4.41 (d, J = 6.1 Hz, 2H), 7.46 (t, J =7.6 Hz, 1H), 7.55 (d, J = 7.6 Hz. 1H), 7.78-7.86 (m, 4H), 7.91 (s, 1H),8.01 (d, J = 8.1 Hz, 2H), 8.20 (d, J = 8.1 Hz, 1H), 8.31 (d, J = 1.0 Hz,1H), 8.94 (t, J = 5.8 Hz, 1H), 12.94 (br s, 1H). II-1-218

1H-NMR (DMSO-d6) δ: 2.29 (s, 3H), 4.11 (s, 2H), 4.40 (d, J = 5.6 Hz,2H), 6.84 (t, J = 7.3 Hz, 2H), 6.97 (d, J = 7.1 Hz, 1H), 7.17 (d, J =9.1 Hz, 1H), 7.27 (t, J = 7.6 Hz, 1H), 7.46 (t, J = 7.1 Hz, 1H), 7.55(d, J = 8.1 Hz, 1H), 7.71 (s, 1H), 7.83 (d, J = 7.1 Hz, 1H), 7.90-7.96(m, 2H), 8.93 (br s, 1H), 12.79 (br s, 1H). II-1-219

1H-NMR (DMSO-d6) δ: 4.16 (s, 2H), 4.40 (d, J = 5.6 Hz, 2H), 7.46 (t, J =7.6 Hz, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.58 (dd, J = 8.6, 2.0 Hz, 1H),7.83 (d, J = 7.6 Hz, 1H), 7.89 (s, 1H), 8.05 (d, J = 8.6 Hz, 1H), 8.17(d, J = 2.0 Hz, 1H), 8.93 (t, J = 5.8 Hz, 1H), 12.94 (br s, 1H).

TABLE 44 retention No. Structure NMR(δ) time Mass method II-1-220

1H-NMR (DMSO-d6) δ: 1.12-1.45 (m, 4H), 1.81- 1.98 (m, 4H), 2.10-2.24 (m,1H), 3.45-3.66 (m, 1H), 4.03 (s, 2H), 7.39 (dd, J = 7.4, 3.7 Hz, 1H),7.50 (t, J = 7.6 Hz, 2H), 7.83-7.70 (m, 3H), 8.00 (d, J = 8.6 Hz, 1H),8.30 (d, J = 7.1 Hz, 1H), 8.37 (s, 1H). 3.62 394.75 (ES+) C II-1-221

1H-NMR (DMSO-d6) δ: 0.83-2.19 (m, 10H), 2.98 (t, J = 6.1 Hz, 2H), 4.05(s, 2H), 7.54-7.34 (m, 3H), 7.82-7.71 (m, 3H), 8.00 (d, J = 8.6 Hz, 1H),8.32-8.37 (m, 2H). 3.74 408.75 (ES+) C II-1-222

1H-NMR (DMSO-d6) δ: 1.01-1.44 (m, 4H), 1.68- 2.10 (m, 5H), 2.24-2.36 (m,1H), 4.03 (s, 2H, 7.34-7.53 (m, 3H), 7.71-7.82 (m, 3H), 8.00 (d, J = 8.1Hz, 1H), 8.30-8.40 (m, 2H). 3.72 394.75 (ES+) C II-1-223

1H-NMR (DMSO-d6) δ: 4.26 (s, 2H), 4.43 (d, J = 6.1 Hz, 2H), 7.46 (t, J =7.6 Hz, 1H), 7.56-7.64 (m, 2H), 7.70 (t, J = 6.8 Hz, 1H), 7.84 (d, J =7.6 Hz, 1H), 7.91-7.93 (m, 2H), 8.07 (d, J = 8.1 Hz, 1H), 8.12 (d, J =8.6 Hz, 1H), 8.64 (d, J = 8.1 Hz, 1H), 8.97 (t, J = 5.8 Hz, 1H), 12.95(br s, 1H). II-1-224

1H NMR (DMSO-d6) δ: 1.54 (s, 9H), 3.82 (s, 2H), 4.38 (d, J = 5.6 Hz,2H), 7.06-7.20 (m, 2H), 7.58, 7.40 (m, 4H), 7.78 (d, J = 7.6 Hz, 1H),7.83 (s, 1H), 8.81 (t, J = 5.8 Hz, 1H), 12.26 (s, 1H).

TABLE 45 retention No. Structure NMR(δ) time Mass method II-1-225

1H-NMR (DMSO-d6) δ: 4.17 (s, 2H), 4.64 (d, J = 6.0 Hz, 2H), 7.39 (t, J =7.4 Hz, 1H), 7.50 (t, J = 7.5 Hz, 2H), 7.64 (d, J = 3.2 Hz, 1H),7.73-7.81 (m, 4H), 8.02 (d, J = 8.4 Hz, 1H), 8.39 (d, J = 1.5 Hz 1H),9.25 (br s, 1H). II-1-226

1H-NMR (DMSO-d6) δ: 1.54 (s, 9H), 3.76 (s, 3H), 3.95 (s, 2H), 4.37 (d, J= 5.6 Hz, 2H), 7.26-7.12 (m, 2H), 7.58-7.41 (m, 4H), 7.78 (d, J = 7.6Hz, 1H), 7.83 (s, 1H), 8.85 (t, J = 5.8 Hz, 1H). II-1-227

1H NMR (DMSO-d6) δ: 4.17 (s, 2H), 4.64 (d, J = 5.5 Hz, 2H), 7.39-7.52(m, 3H), 7.76-7.79 (m, 3H), 8.02 (d, J = 8.6 Hz, 1H), 8.39 (s, 2H), 9.10(br s, 1H). II-1-228

1H-NMR (DMSO-d6) δ: 4.23 (s, 2H), 4.43 (d, J = 6.1 Hz, 2H), 7.54-1.44(m, 3H), 7.58 (d, J = 7.6 Hz, 1H), 7.82-7.75 (m, 2H), 7.85 (d, J = 7.6Hz, 1H), 7.92 (s, 1H), 9.06 (t, J = 5.6 Hz, 1H). 0.97 309.65 (ES+) CII-1-229

1H-NMR (DMSO-d6) δ: 3.92 (s, 3H), 4.28 (s, 2H), 4.42 (d, J = 6.1 Hz,2H), 7.42-7.61 (m, 4H), 7.94- 7.73 (m, 4H), 9.05 (t, J = 5.6 Hz, 1H).1.08 323.90 (ES+) C

TABLE 46 re- ten- tion No. Structure NMR(δ) time Mass method II-1-230

1H-NMR (DMSO-d6) δ: 1.88 (d, J = 6.1 Hz, 3H), 4.11 (s, 2H), 4.40 (d, J =4.5 Hz, 2H), 6.39-6.46 (m, 1H), 6.56 (d, J = 16.2 Hz, 1H), 7.46-7.55 (m,3H), 7.82-8.02 (m, 4H), 8.93 (br s, 1H). II-1-231

1H-NMR (DMSO-d6) δ: 4.20 (s, 2H), 4.47 (d. J = 5.7 Hz, 2H), 7.43-7.57(m, 5H), 7.76-7.79 (m, 3H), 8.03-8.08 (m, 3H), 8.38 (s, 1H), 8.57 (d, J= 4.9 Hz, 1H), 9.04 (br s, 1H). II-1-232

1H-NMR (DMSO-d6) δ: 4.11 (s, 2H), 4.57 (d, J = 5.7 Hz, 2H), 7.39-7 42(m, 1H), 7.50 (t, J = 7.5 Hz 2H), 7.74-7.81 (m, 4H), 8.01 (d, J = 8.6Hz, 1H), 8.39 (d, J = 1.7 Hz, 1H), 8.98-9.02 (m, 2H). II-1-233

1H-NMR (DMSO-d6) δ: 4.02 (s, 2H), 4.41 (d, J = 6.1 Hz, 2H), 7.38 (t, J =7.4 Hz, 1H), 7.48 (td. J = 7.6, 2.2 Hz, 3H), 7.57 (d, J = 7.6 Hz, 1H),7.66-7.85 (m, 5H), 7. 95 (d, J = 14.7 Hz, 2H), 8.92 (t, J = 5.8 Hz, 1H),12.97 (br s, 1H). II-1-234

1H-NMR (CDCl3) δ: 1.54 (s, 6H), 3.71 (s, 3H), 4.00 (d, J = 5.1 Hz, 2H),4.14 (s, 2H), 6.76 (s, 1H), 7.34-7.51 (m, 3H), 7.59-7.86 (m, 4H),8.08-8.02 (m, 2H).

TABLE 47 re- ten- tion No. Structure NMR(δ) time Mass method II-1-235

1H-NMR (DMSO-d6) δ: 4.12 (s, 2H), 4.39 (d, J = 6.1 Hz, 2H), 7.05 (d, J =7.6 Hz, 2H), 7.14-7.18 (m, 2H), 7.38-7.55 (m, 5H), 7.83 (d, J = 7.6 Hz,1H), 7.89 (s, 1H), 8.06 (d, J = 8.6 Hz, 1H), 8.91 (t, J = 5.8 Hz, 1H),12.95 (br s, 1H). II-1-236

1H-NMR (DMSO-d6) δ: 4.05 (s, 2H), 4.39 (d, J = 6.1 Hz, 2H), 6.91 (dd, J= 8.6, 2.0 Hz, 1H), 7.28 (d, J = 2.0 Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H),7.54 (d, J = 7.6 Hz, 1H), 7.79 (d, J = 8.6 Hz, 1H), 7.83 (d, J = 7.6 Hz,1H), 7.89 (s, 1H), 8.88 (t, J = 5.8 Hz, 1H), 9.61 (s, 1H), 12.90 (br s,1H). II-1-237

1H-NMR (DMSO-d6) δ: 4.02 (s, 2H), 4.38 (d, J = 6.0 Hz, 2H), 6.29 (dd, J= 8.3, 2.4 Hz), 7.32 (d, J = 2.4 Hz, 1H), 7.47 (t, J = 7.5 Hz, 1H),7.54(d, J = 7.8 Hz, 1H), 7.73 (d, J = 8.7 Hz, 1H),7.81-7.84 (m, 1H), 7.89(s, 1H), 8.88 (t, J = 5.7 Hz, 1H), 9.71 (s, 1H), 12.95 (brs, 1H).II-1-238

1H-NMR (DMSO-d6) δ: 1.30 (dd, J = 6 1, 1.5 Hz, 6H), 4.08 (s, 2H), 4.39(d, J = 6.1 Hz, 2H), 4.67-4.73 (m, 1H), 7.02 (dd, J = 8.6, 2.0 Hz, 1H),7.44-7.55 (m, 3H), 7.82-7.90 (m, 3H), 8.89 (t, J = 5.3 Hz, 1H), 12.94(br s, 1H). II-1-239

1H-NMR (DMSO-d6) δ: 3.54 (s, 2H), 4.14 (s, 2H), 4.33 (d, J = 5.7 Hz,2H), 7.15-7.18 (m, 3H), 7.28 (t, J = 7.8 Hz, 1H), 7.39 (t, J = 7.4 Hz,1H), 7.50 (t, J = 7.5 Hz, 2H), 7.74-7.81 (m, 3H), 8.02 (d, J = 8.7 Hz,1H), 8.38 (s, 1H), 8.86 (br s. 1H).

TABLE 48 retention No. Structure NMR(δ) time Mass method II-1-240

1H-NMR (DMSO-d6) δ: 2.59 (s, 3H), 4.21 (s, 2H), 4.38 (d, J = 5.7 Hz,2H), 7.26 (d, J = 5.0 Hz, 1H), 7.39-7.42 (m, 1H), 7.50 (t, J = 7.6 Hz,2H), 7.76-7.80 (m, 3H), 8.03 (d, J = 8.4 Hz, 1H), 8.39 (s, 1H), 8.64 (d,J = 5.4 Hz, 1H), 9.02 (br s, 1H). II-1-241

1H-NMR (DMSO- d6) δ: 4.16 (s, 2H), 4.41 (d, J = 6.0 Hz, 2H), 7.26-7.52(m, 7H), 7.74-7.82 (m, 3H), 8.01 (d, J = 8.6 Hz, 1H), 8.38 (d, J = 1.5Hz, 1H), 8.94 (br s, 1H). II-1-242

1H-NMR (CDCl3) δ: 1.22-2.43 (m, 5H), 3.18- 3.42 (m, 4H), 3.91-4.02 (m,2H), 4.08 (s, 2H), 7 33-7.77 (m, 7H), 7.99-8.11 (m, 2H). 3.7 367.05(ES+) C II-1-243

1H-NMR (CDCl3) δ: 206-1.47 (m, 5H), 2.84- 4.08 (m, 6H), 7.28-7.52 (m,4H), 7.57-7.77 (m, 3H), 7.98-8.13 (m, 2H). 3.77 353.00 (ES+) C II-1-244

1H-NMR (CDCl3) δ: 4.10, (s, 2H), 4.51 (d, J = 5.6 Hz, 2H), 6.24 (d, J =3.0 Hz, 1H), 6.32 (t, J = 2.5 Hz, 1H), 7.32-7.67 (m, 7H), 7.72 (dd, J =8.4, 1.8 Hz, 1H), 8.08-8.00 (m, 2H). 4.18 349.15 (ES+) C

TABLE 49 retention No. Structure NMR(δ) time Mass method II-1-245

1H-NMR (DMSO-d6) δ: 4.16 (s, 2H), 4.40 (d, J = 6.1 Hz, 2H), 7.30-7.54(m, 8H), 7.59-7.68 (m, 4H), 7.72-7.82 (m, 3H), 8.03 (d, J = 8.6 Hz, 1H),8.36-8.40 (m, 1H), 8.89 (t, J = 5.6 Hz, 1H). 5.46 435.05 (ES+) CII-1-246

1.83 410.00 (ES+) C

TABLE 50 re- ten- tion No. Structure NMR(δ) time Mass method II-2-2

(DMSO-d₆) δ: 4.13 (s, 2H), 4.40 (d, J = 5.58 Hz, 2H), 7.25-7.35 (m, 3H),7.44-7.56 (m, 2H), 7.62 (m, 1H), 7 82-7.90 (m, 3H), 8.00 (d, J = 9.12Hz, 1H), 8.93 (t, J = 5.58 Hz, 1H), 12.96 (brs, 1H). II-2-3

(DMSO-d6) δ: 1.14 (t, J = 7.1 Hz, 3H), 4.10-4.15 (m, 4H), 4.39 (d, J =6.1 Hz, 2H), 7.23 (t, J = 7.1 Hz, 1H), 7.29-7.39 (m, 5H), 7.45 (t, J =7.6 Hz, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.82 (d, J = 7.6 Hz, 1H), 7.91(t, J = 7.1 Hz, 2H), 8.03 (d, J = 2.0 Hz, 1H), 8.91 (t, J = 6.1 Hz, 1H),12.98 (br s, 1H). II-2-4

(DMSO-d6) δ: 2.20 (s, 3H), 4.09 (s, 2H), 4.39 (d, J = 6.08 Hz, 2H), 6.93(d, J = 8.11 Hz, 1H), 7.09-7.15 (m, 2H), 7.23 (m, 1H), 7.35 (d, J = 7.10Hz, 1H), 7.46 (m, 1H), 7.53-7.56 (m, 2H), 7.83 (d, J = 7.60 Hz, 1H),7.91 (m, 2H), 8.91 (t, J = 5.58 Hz, 1H), 12.96 (brs, 1H). II-2-5

(DMSO-d₆) δ: 4.10 (s, 2H), 4.40 (d, J = 5.58 Hz, 2H), 7.09-7.13 (m, 2H),7.17 (dd, J = 8.62, 2.53 Hz, 1H), 7.20-7.28 (m, 2H), 7.43-7.57 (m, 2H),7.69 (d, J = 2.53 Hz, 1H), 7.83 (d, J = 8.11 Hz, 1H), 7.88-7.97 (m, 2H),8.92 (t, J = 5.83 Hz, 1H), 12.96 (brs, 1H). II-2-6

(DMSO-d₆) δ: 2.30 (s, 3H), 4.09 (s, 2H), 4.39 (d, J = 5.58 Hz, 2H), 6.95(d, J = 8.11 Hz, 2H), 7.15 (dd, J = 8.62, 2.53 Hz, 1H), 7.21 (d, J =8.11 Hz, 2H), 7.46 (m, 1H), 7.54 (d, J = 7.60 Hz, 1H), 7.65 (d, J = 2.53Hz, 1H), 7.83 (d, J = 7.60 Hz, 1H), 7.95-7.88 (m, 2H), 8.91 (t, J = 5.83Hz, 1H), 12.95 (brs, 1H).

TABLE 51 re- ten tion No. Structure NMR(δ) time Mass method II-2-7

(DMSO-d6) δ: 4.14 (s, 2H), 4.41 (d, J = 5.58 Hz, 2H), 6.98-6.94 (m, 2H),7.31 (dd, J = 8.87, 2.28 Hz, 1H), 7.46 (m, 1H), 7.55 (d, J = 7.60 Hz,1H), 7.83 (d, J = 7.60 Hz, 1H), 7.91 (s, 1H), 7.96 (d, J = 2.03 Hz, 1H),8.03 (d, J = 9.12 Hz, 1H), 8.47 (d, J = 5.07 Hz, 2H), 8.94 (t, J = 5.83Hz, 1H), 12.96 (brs, 1H). II-2-8

(DMSO-d₆) δ: 2.88 (s, 6H), 4.07 (s, 2H), 4.39 (d, J = 5.58 Hz, 2H), 6.78(d, J = 8.62 Hz, 2H), 6.96 (d, J = 9.12 Hz, 2H), 7.09 (dd, J = 8.62,2.53 Hz, 1H), 7.42- 7.56 (m, 3H), 7.81-7.90 (m, 3H), 8.90 (t, J = 5.83Hz, 1H), 12.96 (brs, 1H). II-2-9

(DMSO-d6) δ: 4.03 (s, 2H), 4.39 (d, J = 5.6 Hz, 2H), 6.86 (t, J = 7.4Hz, 1H), 7.11-7.19 (m, 3H), 7.26 (t, J = 7.9 Hz, 2H), 7.45 (t, J = 7.6Hz, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.67 (d, J = 2.0 Hz, 1H), 7.77-7.83(m, 2H), 7.90 (s, 1H), 8.36 (s, 1H), 8.88 (t, J = 5.8 Hz, 1H), 12.97 (brs, 1H). II-2-10

1H-NMR (DMSO-d6) δ: 4.16 (s, 2H), 4.64 (d, J = 6.1 Hz, 2H), 5.66 (s,2H), 7.40 (d, J = 7.6 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.74-7.80 (m,4H), 8.01 (d, J = 8.6 Hz, 1H), 8.38 (d, J = 1.5 Hz, 1H), 9.12 (s, 1H).II-2-11

(DMSO-d₆) δ: 4.11 (s, 2H), 4.40 (d, J = 6.08 Hz, 2H), 7.02 (d, J = 7.10Hz, 1H), 7.25 (dd, J = 8.62, 2.53 Hz, 1H), 7.43-7.63 (m, 5H), 7.73-7.85(m, 3H), 7.89-8.03 (m, 3H), 8.12 (d, J = 8.11 Hz, 1H), 8.91 (t, J = 5.83Hz, 1H), 12.95 (brs, 1H).

TABLE 52 re- ten- tion No. Structure NMR(δ) time Mass method II-2-12

1H-NMR (DMSO-d6) δ: 4.15 (s, 2H), 4.42 (d, J = 5.1 Hz, 2H), 7.44 (m,3H), 7.77 (m, 3H), 8.01 (d, J = 8.6 Hz, 1H), 8.28-8.35 (m, 1H), 8.91 (s,1H), 13.88 (s, 1H). II-2-13

(DMSO-d6) δ: 4.21 (s, 2H), 4.42 (d, J = 5.6 Hz, 2H), 7.44-7.57 (m, 8H),7.84 (d, J = 7.6 Hz, 1H), 7.91 (s, 1H), 8.01 (d, J = 8.6 Hz, 1H), 8.98(t. J = 5.3 Hz, 1H), 12.96 (br s, 1H). II-2-14

(DMSO-d₆) δ:4.12 (s, 2H), 4.40 (d, J = 6.08 Hz, 2H), 7.25-7.57 (m, 7H),7 80-7.85 (m, 3H), 7.90- 7.94 (m, 2H), 7.99 (d, J = 9.12 Hz, 2H), 8.93(t, J = 5.58 Hz, 1H), 12.96 (brs, 1H). II-2-15

(DMSO-d₆) δ: 1.41-1.78 (brm, 10H), 1.94-2.03 (m, 2H), 4.05 (s, 2H), 4.39(d, J = 6.08 Hz, 2H), 4.54-4.60 (m, 1H), 7.03 (dd, J = 8.62, 2.53 Hz,1H), 7.46 (t, J = 7.60 Hz, 1H), 7.52-7.59 (m, 2H), 7.78-7.85 (m, 2H),7.90 (s, 1H), 8.88 (t, J = 5.58 Hz, 1H), 12.95 (s, 1H). II-2-16

(DMSO-d₆) δ: 1.49-1.93 (brm, 14H), 4.05 (s, 2H), 4.39 (d, J = 5.58 Hz,2H), 4.55 (brs, 1H), 7.02 (d, J = 7.10 Hz, 1H), 7.43-7.59 (m, 3H),7.78-7.91 (m, 3H), 8.88 (t, J = 5.58 Hz, 1H), 12.95 (brs, 1H).

TABLE 53 re- ten- tion No. Structure NMR(δ) time Mass method II-2-17

(DMSO-d6) δ: 4.07 (s, 2H), 4.39 (d, J = 5.6 Hz, 2H), 7.01-7.06 (m, 6H),7.13 (dd, J = 8.9, 2.3 Hz, 1H), 7.31 (t, J = 7.6 Hz, 4H), 7.45 (t, J =7.6 Hz, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.66 (d, J = 2.0 Hz, 1H),7.81-7.89 (m, 3H), 8.90 (t, J = 5.8 Hz, 1H). II-2-18

(DMSO-d6) δ: 3.72 (d, J = 5.6 Hz, 2H), 4.15 (s, 2H), 7.11 (s, 1H), 7.39(t, J = 7.6 Hz, 1H), 7.46-7.52 (m, 3H), 7.74-7.81 (m, 3H), 8.01 (d, J =8.1 Hz, 1H), 8.38 (d, J = 1.5 Hz, 1H), 8.58 (t, J = 5.3 Hz, 1H). II-2-19

(DMSO-d6) δ: 4.16 (s, 2H), 4.41 (d, J = 5.7 Hz, 2H), 7.78 (d, J = 0.9Hz, 1H), 7.82-7.85 (m, 1H), 7.92 (s, 1H), 8.01-8.04 (m, 2H), 8.22-8.25(m, 2H), 8.82 (d, J = 12 Hz, 1H), 8.95 (t, J = 5.4 Hz, 1H), 12.93 (brs,1H). II-2-20

(DMSO-d₆) δ: 4.07 (s, 2H), 4.39 (d, J = 6.08 Hz, 2H), 5.17 (s, 2H), 7.15(dd, J = 9.12, 2.53 Hz, 1H), 7.31-7.56 (m, 7H), 7.72 (d, J = 2.53 Hz,1H), 7.81-7.86 (m, 2H), 7.90 (s, 1H), 8.90 (t, J = 5.83 Hz, 1H) 12.96(brs. 1H). II-2-21

1H-NMR(DMSO-d6) δ: 3.08 (t, J = 6.6 Hz, 2H), 3.51-3.53 (m, 2H), 4.05 (s,2H), 7 39-7.50 (m, 3H), 7.75-7.79 (m, 3H), 8.01 (d, J = 8.6 Hz, 1H),8.38 (s, 1H), 8.56 (s, 1H), 16.04 (s, 1H).

TABLE 54 re- ten- tion No. Structure NMR(δ) time Mass method II-2-22

(CDCl3) δ: 1.29 (t, J = 7.1 Hz, 3H), 4.09 (s, 2H), 4.26 (q, J = 7.1 Hz,2H), 4.63 (d, J = 5.6 Hz, 2H), 5.12 (s, 2H), 7.38 (t, J = 7.4 Hz, 1H),7.45-7.49 (m, 2H), 7.62-7.64 (m, 2H), 7.70- 7.73 (m, 2H), 7.83 (br s,1H), 8.03-8.06 (m, 2H). II-2-23

(DMSO-d6) δ: 2.41 (s, 3H), 4.15 (s, 2H), 4.41 (d, J = 5.7 Hz, 2H),7.32-7 56 (m, 8H), 7.84 (d J = 7.5 Hz, 1H), 7.91 (s, 1H), 8.02 (d, J =6.3 Hz, 1H), 8.04 (s, 1H), 8.82 (d, J = 0.9 Hz, 1H), 8.94 (t, J = 5.7Hz, 1H), 12.96 (brs, 1H). II-2-24

(DMSO-d6) δ: 4.16 (s, 2H), 4.41 (d, J = 5.7 Hz, 2H), 7.38-7.62 (m, 5H),7.82 (d J = 7.8 Hz, 1H), 7.91 (d, J = 6.9 Hz, 1H), 8.03 (dd, J = 5.7,2.8 Hz, 2H), 857 (d, J = 2.8 Hz, 1H), 8.75 (d, J = 4.5 Hz, 1H), 8.86 (s,1H), 8.95 (t, J = 5.7 Hz, 1H), 9.40 (s, 1H), 12.96 (brs, 1H). II-2-25

(DMSO-d6) δ: 2.33 (s, 3H), 4.12 (s, 2H), 4.39 (d, J = 6.1 Hz, 2H),7.19-7.35 (m, 5H), 7.46 (t, J = 7.6 Hz, 1H), 7.54 (d, J = 7.6 Hz, 1H),7.83 (d, J = 7.6 Hz, 1H), 7.89-7.94 (m, 2H), 7.99 (d, J = 1.5 Hz, 1H),8.93 (t, J = 6.1 Hz, 1H), 12.96 (br s, 1H). II-2-26

(DMSO-d6) δ: 4.12 (s, 2H), 4.40 (d, J = 5.6 Hz, 2H), 5.24 (s, 2H), 7.39(t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.74-7.80 (m, 3H),7.96-8.02 (m, 2H), 8.37 (d, J = 2.0 Hz, 1H), 8.91 (t, J = 5.6 Hz, 1H).

TABLE 55 re- ten- tion No. Structure NMR(δ) time Mass method II-2-27

(DMSO-d6) δ: 2.40 (s, 3H), 4.16 (s, 2H), 4.41 (d, J = 5.6 Hz, 2H), 7.21(d, J = 7.6 Hz, 1H), 7.38 (t, J = 7.6 Hz, 1H), 7.47 (t, J = 7.9 Hz, 1H),7.55-7.57 (m, 3H), 7.72 (dd, J = 8.4, 1.8 Hz, 1H), 7.83 (d, J = 7.6 Hz,1H), 7.91 (s, 1H), 8.13 (d, J = 8.1 Hz, 1H), 8.19 (d, J = 1.5 Hz, 1H),8.95 (t, J = 5.8 Hz, 1H), 12.95 (br s, 1H). II-2-28

1H-NMR(DMSO-d6) δ: 4.17 (s, 2H), 4.38 (d, J = 6.1 Hz, 2H), 7.11-7.24 (m,3H), 7.43-7.48 (m, 8H), 7.76-7.80 (m, 3H), 8.02 (d, J = 8.6 Hz, 1H),8.40 (s, 1H), 8.96-8.99 (m, 1H), 9.95 (s, 1H). II-2-29

(DMSO-d₆) δ: 4.17 (s, 2H), 4.56 (d, J = 5.58 Hz, 2H), 6.76 (s, 1H), 7.39(m, 1H), 7.47-7.53 (m, 2H), 7.73-7.82 (m, 3H), 8.03 (d, J = 8.11 Hz,1H), 8.39 (d, J = 1.01 Hz, 1H), 9.08 (t, J = 5.83 Hz, 1H). II-2-30

(DMSO-d₆) δ: 2.20 (s, 3H), 4.09 (s, 2H), 4.39 (d, J = 6.08 Hz, 2H), 6.93(d, J = 8.11 Hz, 1H), 7.08-7.15 (m, 2H), 7.23 (m, 1H), 7.34 (d, J = 7.60Hz, 1H), 7.46 (m, 1H), 7.52-7.56 (m, 2H), 7.83 (d, J = 7.60 Hz, 1H),7.88-7.94 (m, 2H), 8.91 (t, J = 5.83 Hz, 1H), 12.96 (s, 1H). II-2-31

1H-NMR(DMSO-d6) δ: 3.62-3.67 (m, 5H), 4.17 (s, 2H), 4.36 (d, J = 6.0 Hz,2H), 7.18-7.22 (m, 3H), 7.29-7.32 (m, 1H), 7.42- 7.44 (m, 1H), 7.53 (t,J = 7.7 Hz, 2H), 7.78-7.82 (m, 3H), 8.04 (d, J = 8.6 Hz, 1H), 8.41 (s,1H), 8.89-8.92 (m, 1H).

TABLE 56 re ten- tion- No. Structure NMR(δ) time Mass method II-2-32

(DMSO-d6) δ: 1.19 (d, J = 6.59 Hz, 6H), 3.22 (m, 1H), 4.09 (s, 2H), 4.39(d, J = 5.58 Hz, 2H), 6.90 (m, 1H), 7.10 (dd, J = 9.12, 2.53 Hz, 1H),7.16-7.25 (m, 2H), 7.407.48- (m, 2H), 7.52- 7.58 (m, 2H), 7.83 (d, J =7.60 Hz, 1H), 7.88-7.94 (m, 2H), 8.91 (t, J = 5.83 Hz, 1H), 12.96 (brs,1H). II-2-33

(DMSO-d6) δ: 4.22 (s, 2H), 4.43 (d, J = 5.7 Hz, 2H), 7.39-7.58 (m, 6H),7.77-7.89 (m, 5H), 7.91 (s, 1H), 8.39 (d, J = 1.5 Hz, 1H), 8.98 (t, J =5.7 Hz, 1H), 12.96 (brs, 1H). II-2-34

1H-NMR (DMSO-d6) δ: 4.51 (s, 2H), 7.45-7.53 (m, 3H), 7.68-7.86 (m, 3H),8.04-8 07 (m, 1H), 8.46 (s, 1H), 12.55 (s, 1H). II-2-35

(DMSO-d6) δ: 4.16 (s, 2H), 4.40 (d, J = 5.7 Hz, 2H), 7.38-7.55 (m, 9H),7.82-7.85 (m, 4H), 7.89- 7.91 (m, 3H), 8.38 (d, J = 1.5 Hz, 1H), 8.93(t, J = 5.4 Hz 1H), 12.86 (brs, 1H). II-2-36

(CDCl3) δ: 3.92 (s, 3H), 4.16 (s, 2H), 4.71 (d, J = 5.6 Hz, 2H), 7.39(t, J = 7.6 Hz, 1H), 7.48 (t, J = 7.4 Hz, 2H), 7.64 (d, J = 7.6 Hz, 2H),7.74 (d, J = 8.6 Hz, 1H), 8.06-8.08 (m, 2H), 8.16 (br s, 1H), 8.19 (s,1H).

TABLE 57 re- ten- tion No. Structure NMR(δ) time Mass method II-2-37

(DMSO-d6) δ: 4.23 (s, 2H), 4.43 (d, J = 5.6 Hz, 2H), 7.09-7.59 (m, 13H),7.84 (d, J = 7.6 Hz, 1H), 7.91 (s, 1H), 8.09 (s, 1H), 8.99 (t, J = 5.6Hz, 1H). II-2-38

1H-NMR (DMSO-d6) δ: 3.90 (s, 3H), 4.17 (s, 2H), 4.31 (d, J = 5.7 Hz,2H), 6.99 (d, J = 8.6 Hz, 1H), 7.45-7.52 (m, 4H), 7.73- 7.96 (m, 4H),8.04 (d, J = 8.4 Hz, 1H), 8.41-8.41 (m, 1H), 8.89-8.91 (m, 1H), 10.45(s, 1H). II-2-39

1H-NMR (DMSO-d6) δ: 3.82 (s, 3H), 4.15 (s, 2H), 4.32 (d, J = 5.7 Hz,2H), 7.11 (d, J = 8.7 Hz, 1H), 7.42-7.63 (m, 5H). 7.78- 7.82 (m, 3H),8.04 (d. J = 8.4 Hz, 1H), 8.40 (s, 1H), 8.88 (t, J = 5.8 Hz, 1H), 12.63(s, 1H). II-2-40

1H-NMR (DMSO-d6) δ: 3.57 (s, 2H), 4.19 (s, 2H), 4.37 (d, J = 5.5 Hz,2H), 7.19-7.31 (m, 5H), 7.83- 7.88 (m, 3H), 8.04 (d, J = 8.1 Hz, 2H),8.23 (d, J = 8.2 Hz, 2H), 8.34 (s, 1H), 8.92 (s, 1H), 12.39 (s, 1H).II-2-41

1H-NMR (CDCl3) δ: 1.38-1.45 (m, 11H), 1.67- 1.69 (m, 3H), 2.17-2.19 (m,2H), 2.94-2.97 (m, 2H), 3.11 (s, 2H), 3.23 (t, J = 6.3 Hz, 2H), 4.08 (s,2H), 7.38- 7.40 (m, 2H), 7.48 (t, J = 7.6 Hz, 2H), 7.64 (d, J = 7.6 Hz,2H), 7.73 (dd, J = 8.6, 1.5 Hz, 1H), 8.05 (dd, J = 11.7, 5.1 Hz, 2H).

TABLE 58 re- ten- tion No. Structure NMR(δ) time Mass method II-2-42

(DMSO-d6) δ: 4.17 (s, 2H), 4.50 (d, J = 5.6 Hz, 2H), 7.39 (t, J = 7.4Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.74-7 80 (m, 3H), 8.02 (d, J = 8.6Hz, 1H), 8.38 (d, J = 1.0 Hz, 1H), 8.64 (s, 1H), 9.11 (br s, 1H).II-2-43

(DMSO-d6) δ: 4.17 (s, 2H), 4.38 (d, J = 5.7 Hz, 2H), 6.53 (d, J = 15.3Hz, 1H), 7.35-7.42 (m, 3H), 7.52 (t, J = 7.5 Hz, 2H), 7.63 (d, J = 9.6Hz, 2H), 7.74-7.81, (m, 3H), 8.04 (d, J = 5.4 Hz, 1H), 8.37 (t, J = 1.2Hz, 1H), 8.89 (t. J = 5.7 Hz, 1H), 12.41 (brs, 1H). II-2-44

(CDCl3) δ: 1.35 (t, J = 7.1 Hz, 3H), 4.17 (s, 2H), 4.34 (q, J = 7.1 Hz,2H), 4.83 (d, J = 6.1 Hz, 2H), 7.39 (t, J = 7.4 Hz, 1H), 7.48 (t, J =7.4 Hz, 2H), 7.64 (d. J = 7.1 Hz, 2H), 7.74 (dd, J = 8.6. 1.5 Hz, 1H),8.04-8.08 (m, 2H), 8.29 (s, 1H), 8.32 (br s, 1H). II-2-45

(DMSO-d6) δ: 301-306 (m, 3H), 3.74-3.78 (m, 3H), 4.11-4.22 (m, 6H), 7.38(t, J = 7.2 Hz, 1H), 7.47 (t, J = 7.8 Hz, 2H), 7.63 (d, J = 7.5 Hz, 2H),7.71 (dd, J = 9.0, 2.1 Hz, 2H), 8.02-8.10 (m, 2H) II-2-46

(DMSO-d6) δ: 4.15 (s, 2H), 4.32 (d, J = 5.7 Hz, 2H), 4.63 (s, 2H),6.77-6.80 (m, 1H), 6.88-6.91 (m, 2H), 7.23 (t, J = 7.8 Hz, 1H), 7.39 (t,J = 7.5 Hz, 1H), 7.50 (t, J = 7.2 Hz, 2H), 7.74-7.81 (m, 3H), 8.03 (d, J= 5.7 Hz, 1H), 8.37 (d, J = 1.5 Hz, 1H), 8.85 (t, J = 5.7 Hz, 1H), 12.96(brs, 1H).

TABLE 59 re- ten- tion No. Structure NMR(δ) time Mass method II-2-47

(DMSO-d6) δ: 4.15 (s, 2H), 4.32 (d, J = 5.7 Hz, 2H), 4.64 (s, 2H),6.77-6.81 (m, 1H), 6.88-6.91 (m, 2H), 7.24 (t, J = 7.5 Hz, 1H),7.74-7.81 (m, 3H), 8.03 (d, J = 5.4 Hz, 1H), 8.38 (d, J = 1.5 Hz, 1H),8.67 (t, J = 5.4 Hz, 1H), 12.96 (brs, 1H). II-2-48

(CDCl3) δ: 1.19-1.28 (m, 3H), 4.08-4.26 (m, 4H), 4.41 (d, J = 17 Hz,2H), 4.83 (d, J = 23 Hz, 2H), 7.18- 7.23 (m, 2H), 737-7.49 (m, 4H),7.63-7.71 (m, 4H), 7.96-8.06 (m, 2H), 8.49- 8.58 (m, 1H) II-2-49

(DMSO-d₆) δ: 1.32 (t, J = 7.10 Hz, 3H) 4.40 (q, J = 7.10 Hz, 2H), 4.21(s, 2H), 4.74 (d, J = 5.58 Hz, 2H), 7.39 (m, 1H), 7.50 (t, J = 7.60 Hz,2H), 7.73-7.82 (m, 3H), 8.02 (d, J = 8.11 Hz, 1H). 8.39 (d, J = 1.01 Hz,1H), 9.28 (t, J = 5.58 Hz, 1H). II-2-50

(CDCl3) δ: 1.40 (s, 9H), 3.30 (m, 2H), 4.07 (s, 2H), 4.96 (br-s, 1H),7.38-7.50, (m, 4H), 7.62-7.73 (m, 3H), 8.05-8.08 (m, 2H). II-2-51

(CDCl3) δ: 2.91 (s, 3H), 3.04 (m, 2H), 3.24 (q, J = 6.0 Hz, 2H), 4.08(s, 2H), 7.10 (br-s, 1H), 7.39 (t, J = 7.5 Hz, 1H), 7.50 (t, J = 8.1 Hz,2H), 7.73-7.81 (m, 3H), 8.02 (d, J = 8.7 Hz, 1H), 8.38 (s, 1H), 8.47(br- s, 1H)

TABLE 60 re- ten- tion No. Structure NMR(δ) time Mass method II-2-52

(DMSO-d6) δ: 1.80 (s, 3H), 3.11-3.18 (m, 4H), 4.06 (s, 2H), 7.39 (t, J =6.6 Hz, 1H), 7.49 (t, J = 8.1 Hz, 2H), 7.73-7.80 (m, 3H), 7.91 (m, 1H),8.06 (d, J = 8.4 Hz, 1H), 8.38 (s, 1H), 8.42 (m, 1H) II-2-53

(DMSO-d6) δ: 3.57 (d, J = 5.07 Hz, 2H), 4.13 (s, 2H), 7.38 (m, 1H),7.46-7.52 (m, 2H), 7.73-7.80 (m, 3H), 8.00 (d, J = 8.62 Hz, 1H), 8.18(t, J = 5.07 Hz, 1H), 8.36 (d, J = 1.52 Hz, 1H). II-2-54

(DMSO-d6) δ: 3.85 (d, J = 5.7 Hz, 2H), 4.18 (s, 2H), 7.78-7.86 (m, 4H),7.98- 8.02 (m, 3H), 8.20 (d, J = 8.4 Hz, 1H), 8.31 (s, 1H), 8.72 (m, 1H)II-2-55

1H-NMR (DMSO-d6) δ: 2.57-2.97 (m, 2H), 3.46- 3.50 (m, 2H), 4.16 (s, 2H),4.40 (d, J = 5.6 Hz, 2H), 6.67-6.88 (m, 1H), 7.41- 7.49 (m, 6H), 7.71-7.80 (m, 5H), 8.02 (d, J = 8.1 Hz, 1H), 8.38 (s, 1H), 8.58-8.59 (m, 1H),8.95- 8.97 (m, 1H), 11.82-12.00 (m, 1H). II-2-56

1H-NMR (DMSO-d6) δ: 4.17 (s, 2H), 4.39 (d, J = 5.7 Hz, 2H), 7.42-7 55(m, 6H), 7 78-7.84 (m, 5H), 8.05 (d, J = 8.7 Hz, 1H), 8.40 (s, 1H), 8.96(s, 1H), 13.30 (s, 1H).

TABLE 61 retention No. Structure NMR(δ) time Mass Method II-2-57

2.12 432.95 C II-2-58

(DMSO-d6) δ: 3.83(s, 3H), 4.09(s, 2H), 4.41(d, J = 5.7 Hz, 2H),7.33-7.38 (m, 1H), 7.41-7.56(m, 6H), 7.79(d, J = 5.7 Hz, 2H), 7.83(d, J= 7.8 Hz, 1H), 7.91(s, 1H), 8.91(t, J = 5.7 Hz, 1H), 12.96(brs. 1H).II-2-59

(DMSO-d6) δ: 2.20(s, 3H), 3.81(d, J = 6.0 Hz, 2H), 4.09(s, 2H), 4.16(d,J = 5.7 Hz, 2H), 6.93(d, J = 7.8 Hz, 1H), 7.08-7.15(m, 2H), 7.23(t, J =8.1 Hz, 1H), 7.34(d, J = 7.2 Hz, 1H), 7.54(s, 1H), 7.92(d, J = 9.0 Hz,1H), 8.66-8.69(m, 2H) II-2-60

(DMSO-d6) δ: 2.89(q, J = 6.0 Hz, 2H), 3.18(q, J = 6.0 Hz, 2H), 4.03(s,2H), 7.39-7.81(m, 6H), 7.99- 8.02(m, 2H), 8.19(m, 1H), 8.37(s, 1H),8.43(m, 1H), 8.82(d, J = 6.0 Hz, 1H), 8.95(s, 1H) II-2-61

(DMSO-d6) δ: 4.20(s, 2H), 4.41(d, J = 5.7 Hz, 2H), 7.38-7.48(m, 2H),7.53(t, J = 6.6 Hz, 3H), 7.8-7.92(m, 5H), 8.04(s, 1H), 8.32(s, 1H),8.71-8.89 (m, 2H), 8.95(t, J = 5.7 Hz, 1H), 9.34(s, 1H).

TABLE 62 reten- tion meth- No. Structure NMR(δ) time Mass od II-2-62

(DMSO-d₆) δ: 3.66(d, J = 6.08 Hz, 2H), 3.82(d, J = 5.58 Hz, 2H), 4.17(s,2H), 7.09(s, 1H), 7.25(s, 1H), 7.39(m, 1H), 7.47-7.52(m, 2H),7.73-7.81(m, 3H), 8.01(d, J = 8.62 Hz, 1H), 8.23(t, J = 5.83 Hz, 1H),8.38(d, J = 1.01 Hz, 1H), 8.69(t, J = 5.58 Hz, 1H). II-2-63

1H-NMR (DMSO-d6) δ: 3.10(t, J = 7.1 Hz, 2H), 3.60-3.61(m, 2H), 4.16(s,2H), 4.39(d, J = 6.1 Hz, 2H), 7.37-7.51(m, 5H), 7.75(tt, J = 19.3, 6.5Hz, 5H), 8.2(d, J = 8.6 Hz, 1H), 8.38(s, 1H), 8.64-8.65 (m, 1H), 8.92(t,J = 5.6 Hz, 1H). II-2-64

(DMSO-d₆) δ: 2.65(t, J = 6.34 Hz, 2H), 3.33(dt, J = 6.34, 5.58 Hz, 2H),3.79(d, J = 6.08 Hz, 2H), 4.16(s, 2H), 7.39(m, 1H), 7.47- 7.52(m, 2H),7.73-7.81(m, 3H), 8.01(d, J = 8.62 Hz, 1H), 8.34(t, J = 5.58 Hz, 1H),8.38(d, J = 1.01 Hz, 1H), 8.67(t, J = 5.58 Hz, 1H). II-2-65

(DMSO-d₆) δ: 1.31(t, J = 7.10 Hz, 3H), 2.20(s, 3H), 4.14(s, 2H), 4.40(q,J = 7.27 Hz, 2H), 4.72(d, J = 5.58 Hz, 2H), 6.93(d, J = 8.11 Hz, 1H),7.09-7.15 (m, 2H), 7.23(m, 1H), 7.34 (d, J = 7.60 Hz, 1H), 7.54 (d, J =2.53 Hz, 1H), 7.92 (d, J = 9.12 Hz, 1H), 9.25 (t, J = 5.58 Hz, 1H).II-2-66

(DMSO-d₆) δ: 2.20(s, 3H), 3.55(d, J = 5.07 Hz, 2H), 4.06(s, 2H), 6.92(d,J = 8.11 Hz, 1H), 7.06-7.14 (m, 2H), 7.22(m, 1H), 7.34 (d, J = 7.60 Hz,1H), 7.53 (d, J = 2.53 Hz, 1H), 7.90 (d, J = 8.62 Hz, 1H), 8.15 (t, J =5.07 Hz, 1H).

TABLE 63 retention No. Structure NMR(δ) time Mass method II-2-67

(DMSO-d₆) δ: 1.13(dd, J = 8.36, 5.32 Hz, 2H), 1.49 (dd, J = 8.36, 5.32Hz, 2H), 3.78(d, J= 5.58 Hz, 2H), 4.16(s, 2H), 7.39(m, 1H), 7.47-7.52(m,2H), 7.74- 7.81(m, 3H), 8.01(d, J = 8.62 Hz, 1H), 8.38(d, J = 1.01 Hz,1H), 8.68(t, J = 5.58 Hz, 1H), 8.92(s, 1H). II-2-68

(DMSO-d₆) δ: 4.21(s, 2H), 4.71(d, J = 5.58 Hz, 2H), 7.39(m, 1H), 7.47-7.52(m, 2H), 7.73-7.82(m, 3H), 8.02(d, J = 8.62 Hz, 1H), 8.10(brs, 1H),8.31 (brs, 1H), 8.39(d, J = 1.52 Hz, 1H), 9.26(t, J = 5.58 Hz, 1H).II-2-69

(DMSO-d₆) δ: 4.10(d, J = 6.08 Hz, 2H), 4.19(s, 2H), 7.23(d, J = 3.55 Hz,1H), 7.39(m, 1H), 7.46-7.53(m, 3H), 7.73-7.82(m, 3H), 8.04(d, J = 8.62Hz, 1H), 8.39(s, 1H), 8.81(t, J = 5.58 Hz, 1H), 12.21(s, 1H). II-2-70

(DMSO-d₆) δ: 4.02(d, J = 5.58 Hz, 2H), 4.20(s, 2H), 7.34-7.41(m, 2H),7.47- 7.52(m, 2H), 10.27(s, 1H), 7.73-7.81(m, 3H), 8.00- 8.04(m, 2H),8.28(m, 1H), 8.39(d, J = 1.52 Hz, 1H), 8.74(d, J = 2.53 Hz, 1H), 8.79(t,J = 5.83 Hz, 1H). II-2-71

1H-NMR (DMSO-d6) δ: 1.19-1.24(m, 2H), 1.57- 1.68(m, 3H), 2.99-3.03(m,4H), 3.36-3.39(m, 2H), 4.05(s, 2H), 7.39(t, J = 7.4 Hz, 1H), 7.50(t, J =7.6 Hz, 2H), 7.76-7.78(m, 3H), 8.00(d, J = 8.6 Hz, 1H), 8.37-8.43(m,2H).

TABLE 64 retention No. Structure NMR(δ) time Mass method II-2-72

(DMSO-d6) δ: 3.75(s, 3H), 4.12(s, 2H), 4.25(d, J = 5.7 Hz, 2H),6.84-6.95(m, 3H), 7.37-7.41(m, 3H), 7.74-7.53(m, 3H), 8.02(d, J = 5.7Hz, 1H), 8.38(d, J = 1.6 Hz, 1H), 8.79(t, J = 5.7 Hz, 1H), 12.97(brs,1H). II-2-73

(DMSO-d₆) δ: 1.70(tt, J = 6.25, 7.35 Hz, 2H), 2.48 (t, J = 7.35 Hz, 2H),3.17 (dt, J = 6.25, 5.58 Hz, 2H), 3.75(d, J = 5.58 Hz, 2H), 4.15(s,2.0H), 7.39(m, 1.0H), 7.47-7.52(m, 2.0H), 7.73-7.81(m, 3.0H), 8.01 (d, J= 8.11 Hz, 1.0H), 8.04 (t, J = 5.58 Hz, 1.0H), 8.38 (t, J = 1.01 Hz,1.0H), 8.64 (t, J = 5.58 Hz, 1.0H). II-2-74

(DMSO-d₆) δ: 1.75(tt, J = 7.10, 6.59 Hz, 2H), 2.54 (t, J = 6.59 Hz, 2H),3.21 (dt, J = 7.10, 5.58 Hz, 2H), 4.06(s, 2H), 7.38(m, 1H), 7.50(m, 1H),7.73-7.81(m, 3H), 8.01(d, J = 8.62 Hz, 1H), 8.38(d, J = 1.01 Hz, 1H),8.46(t, J = 5.58 Hz, 1H). II-2-75

(DMSO-d₆) δ: 1.21-1.70 (br m, 8H), 2.14-2.21(m, 2H), 3.85(d, J = 6.08Hz, 2H), 4.16(s, 2H), 7.39(m, 1H), 7.47-7.52(m, 2H), 7.73-7.81(m, 3H),8.01(d, J = 8.11 Hz, 1H), 8.39(d, J = 3.04 Hz, 2.0H), 8.65(t, J = 5.58Hz, 1.0H). II-2-76

1H-NMR (DMSO-d6) δ: 1.21-1.23(m, 2H), 1.55- 1.59(m, 1H), 1.76(d, J =12.2 Hz, 2H), 2.67(t, J = 11.7 Hz, 2H), 2.83-2.84(m, 3H), 3.06-3.07(m,2H), 3.55(d, J = 11.2 Hz, 2H), 4.08(s, 2H), 7.38-7.40(m, 1H),7.49-7.51(m, 2H), 7.74-7.80(m, 3H), 8.00- 8.02(m, 1H), 8.39-8.43(m, 2H).

TABLE 65 retention No. Structure NMR(δ) time Mass method II-2-77

(DMSO-d₆) δ: 2.90-3.09 (m, 3H), 4.11(d, J = 5.58 Hz, 2H), 4.19(s, 2H),4.40- 4.67(m, 2H), 7.39(m, 1H), 7.47-7.52(m, 2H), 7.73- 7.81(m, 3H),8.01(d, J = 8.62 Hz, 1H), 8.38(d, J = 1.01 Hz, 1H), 8.62(t, J = 5.58 Hz,1H) II-2-78

1H-NMR (DMSO-d6) δ: 1.22-1.25(m, 2H), 1.43- 1.55(m, 1H), 1.74-1.76(m,2H), 2.39-2.42(m, 2H), 3.03(t, J = 6.1 Hz, 2H), 3.61(d, J = 11.7 Hz,2H), 4.06(s, 2H), 7.36-7.40(m, 2H), 7.48-7.54(m, 3H), 7.76-7.78(m, 3H),8.00(d, J = 8.6 Hz, 1H), 8.37-8.38 (m, 2H). II-2-79

1H-NMR (DMSO-d6) δ: 1.22-1.25(m, 2H), 1.38- 1.42(m, 1H), 1.63(d, J =11.2 Hz, 2H), 1.97-2.01(m, 2H), 2.78-2.81(m, 4H), 3.02(t, J = 6.1 Hz,2H), 4.07(s, 2H), 7.09-7.11(m, 2H), 7.39(t, J = 7.4 Hz, 1H), 7.50(t, J =7.6 Hz, 2H), 7.74-7.80(m, 3H), 8.00(d, J = 8.6 Hz, 1H), 8.36-8.37(m,2H). II-2-80

1H-NMR (DMSO-d6) δ: 1.16-1.20(m, 2H), 1.37- 1.46(m, 1H), 1.67-1.69(m,2H), 2.07-2.13(m, 2H), 2.70-2.76(m, 2H), 3.03(t, J = 6.3 Hz, 2H),3.68(s, 2H), 4.04(s, 2H), 7.39(t, J = 7.4 Hz, 1H), 7.50(t, J = 7.9 Hz,2H), 7.74-7.80(m, 3H), 8.00(d, J = 8.6 Hz, 1H), 8.36-8.38(m, 2H).II-2-81

1H-NMR (DMSO-d6) δ: 4.13-4.15(m, 2H), 4.39- 4.40(m, 2H), 7.23-7.26(m,2H), 7.43-7.50(m, 4H), 7.75-7.80(m, 3H), 8.02- 8.04(m, 1H), 8.38(s, 1H),8.86-8.87(m, 1H), 10.54- 10.67(m, 1H), 11.29-11.34 (m, 1H).

TABLE 66 retention No. Structure NMR(δ) time Mass method II-2-82

(CDCl3) δ: 3.02-3.21(m, 3H), 4.09-4.32(m, 4H), 1.44-1.46(m, 9H), 7.37(m,1H), 7.47(t, J = 7.5 Hz, 2H), 7.63-7.71(m, 3H), 8.02- 8.07(m, 2H)II-2-83

(DMSO-d6) δ: 3.22(s, 1H), 4.05(s, 2H), 4.17-4.26 (m, 2H), 4.42(s, 2H),7.39 (m, 1H), 7.50(t, J = 7.2 Hz, 2H), 7.74-7.81(m, 3H), 8.01(m, 1H),8.38(s, 1H), 8.66(m, 1H) II-2-84

1H-NMR (DMSO-d6) δ: 1.27(d, J = 3.5 Hz, 3H), 4.15-4.16(m, 4H), 4.33-4.34(m, 1H), 7.39-7.41(m, 1H), 7.49-7.50(m, 2H), 7.76-7.78(m, 3H), 7.99-8.02(m, 1H), 8.38(s, 1H), 8.72-8.74(m, 2H). II-2-85

1H-NMR (DMSO-d6) δ: 1.27(d, J = 7.1 Hz, 3H), 4.14-4.16(m, 4H), 4.33-4.35(m, 1H), 7.38-7.40(m, 1H), 7.50(t, J = 7.6 Hz, 2H), 7.74-7.80(m,3H), 8.01(d, J = 8.6 Hz, 1H), 8.38(d, J = 1.5 Hz, 1H) 8.72-8.74(m, 2H).II-2-86

(CDCl3) δ: 1.46(s, 9H), 4.00-4.14(d, J = 5.1 Hz, 2H), 4.09(s, 2H),7.42(br- s, 1H), 7.59(m, J = 9.3 Hz, 1H), 7.88(d, J = 8.7 Hz, 1H),8.01(s, 1H)

TABLE 67 retention No. Structure NMR(δ) time Mass method II-2-87

(DMSO-d6) δ: 4.10-4.14 (m, 4H), 7.39-7.51(m, 3H), 7.63-7.66(m, 2H),7.74(m, 1H), 8.05-8.09(m, 2H) II-2-88

(DMSO-d6) δ: 3.82(2H, J = 6.0 Hz, dd), 4.15-4.17 (4H, m), 7.63(1H, J =9.3 Hz, d), 7.88(d, J = 9.0 Hz, 1H), 8.36(s, 1H), 8.68-8.74(m, 2H)II-2-89

(DMSO-d₆) δ: 1.43(d, J = 7.60 Hz, 3H), 3.77-3.88(m, 2H), 4.16(s, 2H),4.79(dq, J = 7.60, 7.10 Hz, 1H), 7.39 (m, 1H), 7.47-7.52(m, 2H),7.73-7.81(m, 3H), 8.01(d, J = 8.62 Hz, 1H), 8.38(d, J = 1.52 Hz, 1H),8.70(t, J = 5.83 Hz, 1H), 8.75(d, J = 7.10 Hz, 1H). II-2-90

(DMSO-d₆) δ: 1.43(d, J = 7.60 Hz, 3H), 3.77-3.88(m, 2H), 4.16(s, 2H),4.79(dq, J = 7.60, 7.10 Hz, 1H), 7.39 (m, 1H), 7.47-7.52(m, 2H),7.73-7.81(m, 3H), 8.01(d, J = 8.62 Hz, 1H), 8.38(d, J = 1.52 Hz, 1H),8.70(t, J = 5.83 Hz, 1H), 8.75(d, J = 7.10 Hz, 1H). II-2-91

1H-NMR (DMSO-d6) δ: 4.02(d, J = 5.6 Hz, 2H), 4.20(s, 2H), 7.39(t, J =7.4 Hz, 1H), 7.49-7.55(m, 4H), 7.76-7.79(m, 3H), 8.02(d, J = 8.6 Hz,1H), 8.39-8.44 (m, 3H), 8.80(t, J = 5.6 Hz, 1H), 10.45(s, 1H).

TABLE 68 retention No. Structure NMR(δ) time Mass method II-2-92

(DMSO-d6) δ: 4.24(s, 2H), 4.41(d, J = 6.1 Hz, 2H), 7.41-7.53(m, 7H),7.82(d, J = 7.6 Hz, 1H), 7.89(s, 1H), 8.13(s, 1H), 9.00(t, J = 5.6 Hz,1H). II-2-93

(DMSO-d6) δ: 3.84(d, J = 5.6 Hz, 2H), 4.16(d, J = 5.6 Hz, 2H), 4.25(s,2H), 7.45-7.52(m, 5H), 8.14(s, 1H), 8.70(t, J = 5.3 Hz, 1H), 8.79(t, J =5.6 Hz, 1H). II-2-94

1.8 394.95 (ES+) C II-2-95

2.08 432.90 (ES+) C II-2-96

(DMSO-d6) δ: 2.25(3H, s), 3.83(2H, J = 6.0 Hz, d), 4.16-4.18(4H, m),7.26- 7.32(m, 4H), 7.44(d, J = 8.1 Hz, 1H), 8.03(t, J = 8.4 Hz, 2H),8.69-8.75(m, 2H)

TABLE 69 retention No. Structure NMR(δ) time Mass method II-2-97

(DMSO-d6) δ: 3.83(2H, J = 6.0 Hz, d), 4.16-4.18(4H, m), 7.42(1H, J = 9.3Hz, d), 7.48(1H, J = 7.5 Hz, d), 7.65-7.75(m, 2H), 8.87(d, J = 8.7 Hz,1H), 1H), 7.98- 8.04(m, 2H), 8.69-8.74(m, 2H) II-2-98

1H-NMR (DMSO-d6) δ: 1.37(s, 9H), 2.98-3.00(m, 2H), 3.09-3.11(m, 2H),3.75(d, J = 6.1 Hz, 2H), 4.15(s, 2H), 6.80-6.83(m, 1H), 7.39-7.41(m,1H), 7.48-7.51(m, 2H), 7.74- 7.80(m, 3H), 8.01-8.02(m, 2H), 8.38(d, J =2.0 Hz, 1H), 8.60-8.63(m, 1H). II-2-99

1H-NMR (DMSO-d6) δ: 2.12(s, 6H), 2.27(t, J = 6.8 Hz, 2H), 3.17(q, J =6.3 Hz, 2H), 3.75(d, J = 6.1 Hz, 2H), 4.15(s, 2H), 7.39- 7.41(m, 1H),7.50(t, J = 7.6 Hz, 2H), 7.76-7.79(m, 3H), 7.84-7.87(m, 1H), 8.01(d, J =8.6 Hz, 1H), 8.38(d, J = 2.0 Hz, 1H), 8.62-8.64(m, 1H). II-2-100

(DMSO-d_(d)) δ: 1.12(dd, J = 8.11, 5.58 Hz, 2H), 1.49 (dd, J = 8.11,5.58 Hz, 2H), 3.78(d, J = 5.58 Hz, 2H), 4.18(s, 2H), 7.78-7.87(m, 3H),8.01(d, J = 8.62 Hz, 2H), 8.20(d, J = 8.62 Hz, 1H), 8.31(s, 1H), 8.69(t,J = 5.58 Hz, 1H), 8.92(s, 1H). II-2-101

1H-NMR (DMSO-d6) δ: 2.38(t, J = 7.1 Hz, 2H), 4.05(s, 2H), 4.14(d, J =5.6 Hz, 2H), 7.40-7.41(m, 1H), 7.50(t, J = 7.6 Hz, 2H), 7.75-7.79(m,3H), 8.00(d, J = 8.6 Hz, 1H), 8.37(d, J = 1.5 Hz, 1H), 8.46-8.49(m, 1H),8.63- 8.65(m, 1H).

TABLE 70 retention No. Structure NMR(δ) time Mass method II-2-102

(DMSO-d6) δ: 2.61(s, 6H), 4.17(s, 2H), 4.41(d, J = 5.6 Hz, 2H),7.38-7.49 (m, 6H), 7.55(d, J = 7.6 Hz, 1H), 7.82-7.90(m, 3H), 8.96(t, J= 5.8 Hz, 1H). II-2-103

(DMSO-d6) δ: 4.16(s, 2H), 4.31(d, J = 5.6 Hz, 2H), 4.41(d, J = 6.1 Hz,2H), 7.39(t, J = 7.4 Hz, 1H), 7.45-7.53(m, 4H), 7.74-7.83(m, 5H),8.02(d, J = 8.6 Hz, 1H), 8.38(d, J = 1.5 Hz, 1H), 8.94(t, J = 5.8 Hz,1H), 9.22(t, J = 5.1 Hz, 1H). II-2-104

(DMSO-d₆) δ: 3.65(d, J = 5.58 Hz, 2H), 3.82(d, J = 5.58 Hz, 2H), 4.16(s,2H), 7.39(m, 1H), 7.47-7.52(m, 2H), 7.73-7.81(m, 3H), 8.01(d, J = 8.62Hz, 1H), 8.26(t, J = 5.58 Hz, 1H), 8.38(d, J = 1.52 Hz, 1H), 8.63(t, J =5.32 Hz, 1H), 8.83(s, 1H), 10.48(s, 1H). II-2-105

(DMSO-d6) δ: 2.61(s, 6H), 3.83(d, J = 5.6 Hz, 2H), 4.15-4.18(m, 4H),7.37-7.49(m, 5H), 7.86(s, 1H), 8.69(t, J = 5.6 Hz, 1H), 8.75(t, J = 5.6Hz, 1H). II-2-106

(DMSO-d₆) δ: 2.73(s, 3H), 3.52(d, J = 5.07 Hz, 2H), 3.80(d, J = 6.08 Hz,2H), 4.15(s, 2H), 7.39(m, 1H), 7.47-7.52(m, 3H), 7.69-7.81(m, 4H),8.02(d, J = 8.62 Hz, 1H), 8.38(s, 1H), 8.67(t, J = 5.58 Hz, 1H).

TABLE 71 retention No. Structure NMR(δ) time Mass method II-2-107

1H-NMR (DMSO-d6) δ: 3.86(d, J = 5.6 Hz, 2H), 3.92-3.95(m, 2H), 4.16(s,2H), 7.39-7.41(m, 1H), 7.50(t, J = 7.6 Hz, 2H), 7.74-7.81(m, 3H),8.01(d, J = 8.6 Hz, 1H), 8.38(d, J = 1.5 Hz, 1H), 8.62-8.64 (m, 1H),8.69-8.72(m, 1H). II-2-108

1H-NMR (DMSO-d6) δ: 3.15(q, J = 5.9 Hz, 2H), 3.40-3.41(m, 2H), 3.77(d, J= 5.6 Hz, 2H), 4.15(s, 2H), 4.67-4.69(m, 1H), 7.39-7.41(m, 1H), 7.50(t,J = 7.6 Hz, 2H), 7.75-7.80 (m, 3H), 7.98-8.01(m, 2H), 8.38(d, J = 1.5Hz, 1H), 8.59-8.62(m, 1H). II-2-109

1H-NMR (DMSO-d6) δ: 3.18-3.20(m, 4H), 3.61(s, 2H), 4.06(s, 2H),7.39-7.41 (m, 1H), 7.50(t, J = 7.6 Hz, 2H), 7.76-7.78(m, 3H), 8.01(d, J= 8.1 Hz, 1H), 8.34-8.41(m, 3H). II-2-110

(DMSO-d₆) δ: 3.58(s, 3H), 3.64(d, J = 5.58 Hz, 2H), 3.83(d, J = 5.58 Hz,2H), 4.16(s, 2H), 7.39(m, 1H), 7.47-7.52(m, 2H), 7.73-7.81(m, 3H),8.01(d, J = 8.62 Hz, 1H), 8.29(t, J = 5.58 Hz, 1H), 8.38(s, 1H), 8.66(t,J = 5.32 Hz, 1H), 11.07(brs, 1H). II-2-111

(DMSO-d6) δ: 3.83(2H, J = 6.0 Hz, d), 4.16-4.18(4H, m), 7.83-7.88(m,3H), 8.50 (s, 1H), 8.69-8.75(m, 2H)

TABLE 72 retention No. Structure NMR(δ) time Mass method II-2-112

(DMSO-d6) δ: 3.83(2H, J = 6.0 Hz, d), 4.16-4.18(4H, m), 7.31-7.38(m,2H), 7.44 (m, 1H), 7.58-7.68(m, 2H), 8.03(d, J = 8.1 Hz, 1H), 8.26(s,1H), 8.69-8.74(m, 2H) II-2-113

(DMSO-d6) δ: 3.83(2H, J = 6.0 Hz, d), 4.16-4.18(4H, m), 7.23(t, J = 9.3Hz, 1H), 750-7.64(m, 4H), 7.83(d, J = 9.3 Hz, 1H), 8.02(d, J = 8.4 Hz,1H), 8.45(s, 1H), 8.68-8.76(m, 2H) II-2-114

(DMSO-d6) δ: 3.83(2H, J = 6.0 Hz, d), 4.16-4.18(4H, m), 7.33(t, J = 8.7Hz, 1H), 7.76-7.80(m, 3H), 8.01(d, J = 8.4 Hz, 1H), 8.37(s, 1H),8.69-8.74(m, 2H) II-2-115

1H-NMR (DMSO-d6) δ: 2.39(t, J = 7.1 Hz, 2H), 3.26-3.30(m, 2H), 3.74(d, J= 5.6 Hz, 2H), 4.15(s, 2H), 7.39-7.41(m, 1H), 7.50(t, J = 7.6 Hz, 2H),7.74-7.80(m, 3H), 8.01- 8.03(m, 2H), 8.38(d, J = 1.5 Hz, 1H),8.60-8.63(m, 1H), 12.22-12.24(m, 1H). II-2-116

1H-NMR (DMSO-d6) δ: 3.00(s, 3H), 3.25(t, J = 6.8 Hz, 2H), 3.49-3.51(m,2H), 3.76(d, J = 5.6 Hz, 2H), 4.15(s, 2H), 7.39(t, J = 7.4 Hz, 1H),7.50(t, J = 7.6 Hz, 2H), 7.77(td, J = 9.6, 3.5 Hz, 3H), 8.01(d, J = 8.1Hz, 1H), 8.24(t, J = 5.6 Hz, 1H), 8.38(d, J = 1.5 Hz, 1H), 8.67(t, J =5.8 Hz, 1H).

TABLE 73 retention No. Structure NMR(δ) time Mass method II-2-117

1H-NMR (DMSO-d6) δ: 3.96(d, J = 5.6 Hz, 2H), 4.17(s, 2H), 7.39(t, J =7.1 Hz, 1H), 7.50(t, J = 7.6 Hz, 2H), 7.75-7.81(m, 3H), 8.01(d, J = 8.6Hz, 1H), 8.39(d, J = 1.5 Hz, 1H), 8.85(t, J = 5.6 Hz, 1H). II-2-118

(DMSO-d₆) δ: 3.85(d, J = 6.08 Hz, 2H), 4.15(s, 2H), 7.39(m, 1H),7.47-7.52(m, 2H), 7.73-7.81(m, 3H), 8.01(d, J = 8.11 Hz, 1H), 8.38(d, J= 1.52 Hz, 1H), 8.71(t, J = 5.83 Hz, 1H), 12.64(brs, 1H). II-2-119

(DMSO-d6) δ: 3.83(d, J = 5.7 Hz, 2H), 4.16-4.19(m, 2H), 7.78(t, J = 7.8Hz, 1H), 7.88-7.96(m, 2H), 8.08(d, J = 8.7 Hz, 1H), 8.13(d, J = 7.8 Hz,1H), 8.26(s, 1H), 8.54(s, 1H), 8.67-8.77(m, 2H) II-2-120

(DMSO-d6) δ: 3.27(s, 3H), 3.84(d, J = 5.7 Hz, 2H), 4.16-4.19(m, 4H),7.86-8.09(m, 6H), 8.52(d, J = 5.1 Hz, 1H), 8.63-8.81 (m, 2H) II-2-121

1H-NMR (DMSO-d6) δ: 3.15(s, 3H), 3.85-3.88(m, 2H), 4.16(s, 2H),7.37-7.51 (m, 4H), 7.74-7.80(m, 4H), 8.00-8.02(m, 1H), 8.37- 8.38(m,1H), 8.62-8.63(m, 1H).

TABLE 74 retention No. Structure NMR(δ) time Mass method II-2-122

(DMSO-d6) δ: 1.47(s, 9H), 4.01(d, J = 5.4 Hz, 2H), 4.08-4.16(m, 2H),7.48(br-s, 1H), 7.58(t, J = 7.5 Hz, 1H), 7.65-7.69(m, 2H), 7.87(d, J =9.0 Hz, 1H), 7.91(s, 1H), 8.05(s, 1H), 8.12(d, J = 8.4 Hz, 1H) II-2-123

1H-NMR (DMSO-d6) δ: 3.24-3.25(m, 5H), 3.34- 3.36(m, 1H), 3.77(d, J = 6.1Hz, 2H), 4.15(s, 2H), 7.37-7.41(m, 1H), 7.48- 7.1(m, 2H), 7.76-7.79(m,3H), 8.01-8.04(m, 2H), 8.38(d, J = 1.5 Hz, 1H), 8.62(t, J = 5.8 Hz, 1H).II-2-124

(CDCl₃) δ: 2.95(s, 3H), 3.55(dd, J = 6.08, 5.58 Hz, 2H), 4.07(d, J =5.58 Hz, 2H), 4.15(s, 2H), 4.97(dt, J = 6.08, 6.59 Hz, 1H), 6.27 (t, J =6.59 Hz, 1H), 7.31- 7.44(m, 3H), 7.55(d, J = 7.60 Hz, 2H), 7.63(dd, J =8.11, 1.52 Hz, 1H), 7.91- 7.99(m, 3H), 8.10(t, J = 5.58 Hz, 1H).II-2-125

(DMSO-d6) δ: 3.85(d, J = 5.7 Hz, 2H), 4.17(s, 2H), 7.70(t, J = 7.5 Hz,1H), 7.86 (t, J = 9.0 Hz, 2H), 8.04(d, J = 8.7 Hz, 1H), 8.12(d, J = 8.4Hz, 1H), 8.50(s, 1H), 8.73(m, 1H), 12.61(br-s, 1H) II-2-126

(DMSO-d6) δ: 1.47(s, 9H), 4.01(d, J = 5.4 Hz, 2H), 4.16(s, 2H), 7.48(br-s, 1H), 7.65-7.82(m, 5H), 8.05-8.12(m, 2H)

TABLE 75 retention No. Structure NMR(δ) time Mass method II-2-127

(DMSO-d6) δ: 3.85(d, J = 6.0 Hz, 2H), 4.17(s, 2H), 7.88(d, J = 9.0 Hz,1H), 7.89-7.97(m, 4H), 8.06(d, J = 8.4 Hz, 1H), 8.52(s, 1H), 8.73(s,1H), 12.64 (br-s, 1H) II-2-128

1H-NMR (DMSO-d6) δ: 1.04(s, 6H), 3.05(d, J = 6.1 Hz, 2H), 3.82(d, J =6.1 Hz, 2H), 4.15(s, 2H), 4.44 (s, 1H), 7.39-7.41(m, 1H), 7.50(t, J =7.6 Hz, 2H), 7.74-7.80(m, 4H), 8.02(d, J = 8.6 Hz, 1H), 8.38(d, J = 1.5Hz, 1H), 8.60-8.62 (m, 1H). II-2-129

1H-NMR (DMSO-d6) δ: 1.18(s, 7H), 3.39(d, J = 6.1 Hz, 2H), 3.74(d, J =5.6 Hz, 2H), 4.15(s, 2H), 4.79 (t, J = 5.8 Hz, 1H), 7.37- 7.40(m, 2H),7.50(t, J = 7.6 Hz, 2H), 7.76-7.79(m, 3H), 8.01(d, J = 8.6 Hz, 1H),8.38(d, J = 2.0 Hz, 1H), 8.49-8.52(m, 1H). II-2-130

1H-NMR (DMSO-d6) δ: 1.52-1.59(m, 2H), 3.13- 3.14(m, 2H), 3.40-3.42(m,2H), 3.74(d, J = 5.6 Hz, 2H), 4.15(s, 2H), 4.43(t, J = 5.3 Hz, 1H),7.38-7.40 (m, 1H), 7.48-7.51(m, 2H), 7.74-7.80(m, 3H), 7.93(t, J = 5.3Hz, 1H), 8.01(d, J = 8.6 Hz, 1H), 8.38(d, J = 2.0 Hz, 1H), 8.62(t, J =5.6 Hz, 1H). II-2-131

1H-NMR (DMSO-d6) δ: 1.00-1.05(m, 3H), 3.02- 3.04(m, 2H), 3.64-3.65(m,1H), 3.78(,d J = 5.6 Hz, 2H), 4.15(s, 2H), 4.67(d, J = 4.6 Hz, 1H),7.38-7.40 (m, 1H), 7.48-7.51(m, 2H), 7.74-7.80(m, 3H), 7.91(t, J = 5.8Hz, 1H), 8.01(d, J = 8.1 Hz, 1H), 8.38(d, J = 2.0 Hz, 1H), 8.61(t, J =5.8 Hz, 1H).

TABLE 76 retention No. Structure NMR(δ) time Mass method II-2-132

1H-NMR (DMSO-d6) δ: 1.03 (d, J = 6.6 Hz, 3H), 3.22-3.25 (m, 1H), 3.36-3.37 (m, 0H), 3.76-3.79 (m, 3H), 4.15 (s, 2H), 4.69 (t, J = 5.6 Hz, 1H),7.37-7.41 (m, 1H), 7.48-7.51 (m, 2H), 7.73-7.77 (m, 5H), 8.01 (d, J =8.1 Hz, 1H), 8.38 (d, J = 1.5 Hz, 1H), 8.57 (t, J = 5.6 Hz, 1H).II-2-133

(DMSO-d6) δ: 1.52-1.68 (m, 6H), 3.18 (t, J = 5.3 Hz, 4H), 3.81 (d, J =5.6 Hz, 2H), 4.06 (s, 2H), 4.16 (d, J = 5.6 Hz, 2H), 7.14 (dd, J = 8.9,2.3 Hz, 1H), 7.37 (d, J = 2.5 Hz, 1H), 7.80 (d, J = 8.6 Hz, 1H), 8.68(t, J = 5.3 Hz, 2H). II-2-134

(DMSO-d6) δ: 3.83 (d, J = 6.0 Hz, 2H), 4.16-4.18 (m, 4H), 7.70 (t, J =8.1 Hz, 1H), 7.87 (t, J = 8.4 Hz, 2H), 8.05 (d, J = 8.7 Hz, 1H), 8.12(d, J = 8.7 Hz, 1H), 8.26 (s, 1H), 8.50 (s, 1H). 8.69-8.75 (m, 2H)II-2-135

(DMSO-d6) δ: 3.83 (d, J = 6.0 Hz, 2H), 4.18 (s, 2H), 7.88 (d, J = 8.7Hz, 1H), 7.90-8.04 (m, 4H), 8.06 (d, J = 8.4 Hz, 1H), 8.52 (s, 1H),8.69-8.75 (m, 2H) II-2-136

1H-NMR (DMSO-d6) δ: 1.02 (t, J = 7.1 Hz, 3H), 3.10-3.12 (m, 2H), 3.73(d, J = 5.6 Hz, 2H), 4.15 (s, 2H), 7.40-7.41 (m, 1H), 7.48-7.51 (m, 2H),7.74- 7.81 (m, 3H), 7.96-8.00 (m, 2H), 8.38 (d, J = 15 Hz, 1H), 8.61 (s,1H).

TABLE 77 retention No. Structure NMR(δ) time Mass method II-2-137

1H-NMR (DMSO-d6) δ: 3.36-3.37 (m, 1H), 3.42- 3.44 (m, 1H), 3.79 (d, J =5.6 Hz, 2H), 4.15 (s, 2H), 4.37 (t, J = 5.1 Hz, 1H), 4.49 (t, J = 5.1Hz, 1H), 7.39 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.76-7.79(m, 4H), 8.01 (d, J = 8.1 Hz, 1H), 8.23 (t, J = 5.6 Hz, 1H), 8.38 (d, J= 1.5 Hz, 1H), 8.65 (t, J = 5.8 Hz, 1H). II-2-138

1H-NMR (DMSO-d6) δ: 3.29-3.36 (m, 4H), 7.43 (t, J = 7.4 Hz, 1H), 7.52(t, J = 7.6 Hz, 2H), 7.78-7.79 (m, 2H), 7.93 (dd, J = 8.6, 2.0 Hz, 1H),8.15 (d, J = 8.6 Hz, 1H), 8.53 (d, J = 1.5 Hz, 1H), 9.00 (t, J = 5.6 Hz,1H), 9.57 (s, 1H). II-2-139

(DMSO-d6) δ: 3.81 (d, J = 6.1 Hz, 2H), 4.08 (s, 2H), 4.16 (d, J = 5.6Hz, 2H), 6.85 (t, J = 7.4 Hz, 1H), 7.11-7.17 (m, 3H), 7.26 (t, J = 7.6Hz, 2H), 7.59 (d, J = 2.0 Hz, 1H), 7.86 (d, J = 8.6 Hz, 1 H), 8.33 (s,1H), 8.66-8.69 (m, 2H). II-2-140

(DMSO-d6) δ: 3.82 (d, J = 5.6 Hz, 2H), 4.11 (s, 2H), 4.17 (d, J = 5.6Hz, 2H), 7.34 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.6 Hz, 2H), 7.57-7.60(m, 3H), 7.81 (s, 1H), 8.69 (t, J = 5.6 Hz, 2H). II-2-141

(CDCl3) δ: 1.46 (s, 9H), 3.99 (d, J = 5.1 Hz, 2H), 4.07 (s, 2H), 7.04(d, J = 7.8 Hz, 1H), 7.13-7.41 (m, 6H), 7.51 (m, 1H), 7.97 (d, J = 9.0Hz, 1H)

TABLE 78 retention No. Structure NMR(δ) time Mass method II-2-142

(DMSO-d6) δ: 3.83 (d, J = 6.0 Hz, 2H), 4.10 (s, 2H), 7.04 (d, J = 8.1Hz, 2H), 7.13-7.21 (m, 2H), 7.41 (t, J = 7.5 Hz, 2H), 7.73 (s, 1H), 7.95(d, J = 9.0 Hz, 1H), 8.69 (m, 1H) II-2-143

(DMSO-d6) δ: 3.82 (d, J = 5.7 Hz, 2H), 4.11 (s, 2H), 4.16 (d, J = 5.1Hz, 2H), 7.04 (d, J = 8.7 Hz, 2H), 7.15-7.20 (m, 2H), 7.40 (t, J = 7.8Hz, 2H), 7.73 (s, 1H), 7.95 (d, J = 8.7 Hz, 1H), 8.68-8.71 (m, 2H)II-2-144

(DMSO-d6) δ: 3.81 (s, 2H), 3.84 (s, 2H), 4.13 (s, 2H), 4.18 (d, J = 5.7Hz, 2H), 7.34-7.38 (m, 1H), 7.40-7.45 (m, 2H), 7.50-7.53 (m, 2H), 7.63(s, 1H), 7.94 (s, 1H9, 8.68 (t, J = 6.0 Hz, 1H9, 8.71 (t, J = 6.0 Hz,1H). II-2-145

(DMSO-d6) δ: 3.87 (d, J = 5.7 Hz, 2H), 4.19 (d, J = 5.5 Hz, 2H), 4.25(s, 2H), 7.44-7.56 (m, 3H), 7.81 (d, J = 7.1 Hz, 2H), 7.92 (d, J = 1.7Hz, 1H), 8.42 (d, J = 1.0 Hz, 1H), 8.71 (t, J = 5.5 Hz, 1H), 8.80 (t, J= 6.0 Hz, 1H). II-2-146

(DMSO-d6) δ: 3.17 (q, J = 5.7 Hz, 2H), 3.42 (q, J = 5.7 Hz, 2H), 3.76(d, J = 5.4 Hz, 2H), 4.12 (s, 2H), 4.69 (d, t = 5.4 Hz, 1H), 7.43 (t, J= 6.9 Hz, 2H), 7.50-7.53 (m, 2H), 7.98 (t, J = 5.7 Hz, 1H), 8.58 (t, J =5.7 Hz, 1H).

TABLE 79 retention No. Structure NMR(δ) time Mass method II-2-147

(DMSO-d₆) δ: 3.85 (d, J = 5.58 Hz, 2H), 4.16 (s, 2H), 7.22 (m, 1H),7.50-7.64 (m, 3H), 7.83 (m, 1H), 8.02 (d, J = 8.11 Hz, 1H), 8.45 (d, J =1.01 Hz, 1H), 8.72 (t, J = 5.58 Hz, 1H), 12.64 (brs, 1H). II-2-148

(DMSO-d₆) δ: 3.15 (dt, J = 6.08, 5.32 Hz, 2H), 3.41 (dt, J = 6.08, 5.32Hz, 2H), 3.77 (d, J = 5.58 Hz, 2H), 4.16 (s, 2H), 4.68 (t, J = 5.32 Hz,1H), 7.23 (m, 1H), 7.50-7.64 (m, 3H), 7.83 (m, 1H), 7.96 (t, J = 5.32Hz, 1H), 8.02 (d, J = 8.62 Hz, 1H), 8.45 (s, 1H), 8.61 (t, J = 5.58 Hz,1H). II-2-149

(DMSO-d6) δ: 3.83 (d, J = 6.1 Hz, 2H), 4.16-4.19 (m, 4H), 7.43-7.50 (m,5H), 8.15 (d, J = 5.1 Hz, 2H), 8.69 (t, J = 5.3 Hz, 1H), 8.75 (t, J =5.6 Hz, 1H). II-2-150

(DMSO-d₆) δ: 3.81 (s, 3H), 3.84 (d, J = 5.58 Hz, 2H), 4.14 (s, 2H), 7.05(d, J = 8.62 Hz, 2H), 7.69 (d, J = 8.62 Hz, 2H). 7.74 (dd, J = 8.62,1.52 Hz, 1H), 7.97 (d, J = 8.62 Hz, 1H). 8.31 (d, J = 1.52 Hz, 1H), 8.70(t, J = 5.58 Hz, 1H). 12.63 (brs, 1H). II-2-151

(DMSO-d6) δ: 3.28 (s, 3H), 3.86 (d, J = 6.0 Hz, 2H), 4.18 (s, 2H), 7.88(dd, J = 8.7, 2.1 Hz, 1H), 8.03- 8.08 (m, 5H), 8.52 (d, J = 1.8Hz, 1H),8.73 (m, 1H)

TABLE 80 retention No. Structure NMR(δ) time Mass method II-2-152

(DMSO-d6) δ: 3.27 (s, 3H), 3.84 (d, J = 4.2 Hz, 2H), 4.19 (s, 4H), 7.87(d, J = 5.1 Hz, 1H), 7.90-8.08 (m, 5H), 8.52 (s, 1H), 8.70-8.75 (m, 2H)II-2-153

(DMSO-d6) δ: 3.85 (d, J = 5.7 Hz, 2H), 4.15 (s, 2H), 7.33 (t, J = 8.7Hz, 2H), 7.75-7.79 (m, 3H), 8.01 (d, J = 8.4 Hz, 1H), 8.37 (s, 1H), 8.72(m, 1H) II-2-154

(DMSO-d₆) δ: 3.60 (s, 3H), 3.69 (d, J = 5.07 Hz, 2H), 4.15 (s, 2H), 7.39(m, 1H), 7.47-7.52 (m, 2H), 7.73-7.81 (m, 3H), 8.01 (d, J = 8.62 Hz,1H), 8.38 (d, J = 1.52 Hz, 1H), 8.68 (t, J = 5.07 Hz, 1H), 11.20 (br s,1H). II-2-155

(DMSO-d₆) δ: 3.59-3.73 (m, 5H), 3.82-3.93 (m, 2H), 4.15 (s, 2H), 4.38(dt, J = 7.60, 5.07 Hz, 1H), 5.08 (t, J = 5.83 Hz, 1H), 7.39 (m, 1.0H)7.47-7.52 (m, 2H), 7.73-7.81 (m, 3H), 8.01 (d, J = 8.62 Hz, 1H), 8.31(d, J = 7.60 Hz, 1H), 8.38 (d, J = 1.01 Hz, 1H), 8.62 (t, J = 5.58 Hz,1H). II-2-156

1H-NMR (DMSO-d6) δ: 3.76 (s, 3H), 3.93-3.95 (m, 2H), 4.16 (s, 2H),5.45-5.47 (m, 1H), 7.37-7.41 (m, 1H), 7.48-7.51 (m, 2H), 7.76- 7.79 (m,3H), 8.01 (d, J = 8.6 Hz, 1H), 8.38 (d, J = 1.5 Hz, 1H), 8.70 (t, J =5.8 Hz, 1H), 9.24 (d, J = 9.1 Hz, 1H).

TABLE 81 retention No. Structure NMR(δ) time Mass method II-2-157

1H-NMR (DMSO-d6) δ: 3.50-3.54 (m. 2H), 3.83 (d, J = 5.6 Hz, 2H), 4.16(s, 2H), 5.87-6.15 (m, 1H), 7.37-7.41 (m, 1H), 7.48- 7.51 (m, 2H),7.75-7.79 (m, 3H), 8.01 (d, J = 8.6 Hz, 1H), 8.35-8.38 (m, 2H), 8.68 (t,J = 5.6 Hz, 1H). II-2-158

1H-NMR (DMSO-d6) δ: 2.85 (s, 1.5H), 3.00 (s, 1.5H), 3.35-3.36 (m, 2H),3.46-3.48 (m, 1H), 3.54- 3.55 (m, 1H), 4.02 (d, J = 5.1 Hz, 1H), 4.10(d, J = 5.1 Hz, 1H), 4.18 (d, J = 4.1 Hz, 2H), 4.66 (t, J = 5.6 Hz,0.5H), 4.88 (t, J = 5.3 Hz, 0.5H), 7.39 (t, J = 7.4 Hz, 1H), 7.50 (t, J= 7.9 Hz, 2H), 7.74-7.80 (m, 3H), 8.01 (d, J = 8.6 Hz, 1H), 8.38 (d, J =1.5 Hz, 1H), 8.46-8.47 (m, 1H). II-2-159

1H-NMR (DMSO-d6) δ: 1.24 (d, J = 7.1 Hz, 3H), 3.80-3.89 (m, 2H), 4.16(s, 2H), 4.58-4.62 (m, 1H), 7.38-7.40 (m, 1H), 7.50 (t, J = 7.6 Hz, 2H),7.74-7.80 (m, 3H), 8.01 (d, J = 8.6 Hz, 1H), 8.38 (d, J = 1.5 Hz, 1H),8.52 (d, J = 8.6 Hz, 1H), 8.66 (t, J = 5.8 Hz, 1H) II-2-160

1H-NMR (DMSO-d6) δ: 3.40-3.41 (m, 2H), 3.79 (d, J = 6.1 Hz, 2H), 4.08(t, J = 5.3 Hz, 2H), 4 15 (s, 2H), 7.39 (t, J = 7.4 Hz, 1H), 7.50 (t, J= 7.6 Hz, 2H), 7.74-7.80 (m, 3H), 8.01 (d, J = 8.1 Hz, 1H), 8.25 (t, J =5.6 Hz, 1H), 8.38 (d, J = 1.5 Hz, 1H), 8.66 (t, J = 5.6 Hz, 1H).

TABLE 82 retention No. Structure NMR(δ) time Mass method II-2-161

(DMSO-d₆) δ: 3.15 (dt, J = 6.08, 6.08 Hz, 2H), 3.41 (dt, J = 5.58, 6.08Hz, 2H), 3.76 (d, J = 5.58 Hz, 2H), 3.81 (s, 3H), 4.14 (s, 2H), 4.68 (t,J = 5.83 Hz, 1H), 7.05 (d, J = 8.62 Hz, 2H), 7.70 (d, J = 8.62 Hz, 2H),7.74 (dd, J = 8.36, 1.77 Hz, 1H), 7.94-7.99 (m, 2H), 8.32 (d, J = 1.77Hz, 1H), 8.60 (t, J = 5.58 Hz, 1H). II-2-162

(DMSO-d₆) δ: 3.16 (dt, J = 6.08, 6.08 Hz, 2H), 3.41 (dt, J = 5.58, 6.08Hz, 2H), 3.77 (d, J = 5.58 Hz, 2H), 4.18 (s, 2H), 4.69 (t, J = 6.08 Hz,1H), 7.78-7.87 (m, 3H), 7.95-8.03 (m, 3H), 8.20 (d, J = 8.62 Hz, 1H),8.32 (s, 1H), 8.62 (t, J = 5.58 Hz, 1H). II-2-163

(DMSO-d6) δ: 1.97-2.00 (m, 4H), 3.26-3.30 (m, 4H), 3.81 (d, J = 6.1 Hz,2H), 4.04 (s, 2H), 4.17 (d, J = 5.6 Hz, 2H), 6.75 (dd, J = 8.6, 2.0 Hz,1H). 6.99 (d, J = 2.0 Hz, 1H), 7.76 (d, J = 8.6 Hz, 1H), 8.65-8.69 (m,2H). II-2-164

1H-NMR (DMSO-d6) δ: 3.60-3.66 (m, 2H), 3.86- 3.94 (m, 2H), 4.16 (s, 2H),4.53-4.56 (m, 1H), 5.18 (t, J = 5.8 Hz, 1H), 7.38-7.40 (m, 1H), 7.50 (t,J = 7.6 Hz, 2H), 7.74-7.80 (m, 3H), 8.01 (d, J = 8.6 Hz, 1H), 8.38 (d, J= 1 5 Hz, 1H), 8.50 (d, J = 9.1 Hz, 1H), 8.65 (t, J = 5.6 Hz, 1H).II-2-165

(DMSO-d6) δ: 3.84 (d, J = 5.7 Hz, 2H), 4.17 (d, J = 5.7 Hz, 2H), 4.21(s, 2H), 7.47- 7.56 (m, 3H), 8.12-8.18 (m, 3H), 8.41 (d, J = 8.4 Hz,1H), 8.69 (t, J = 5.7 Hz, 1H), 8.77 (t, J = 5.7 Hz, 1H)..

TABLE 83 retention No. Structure NMR(δ) time Mass method II-2-166

(DMSO-d6) δ: 3.15 (q, J = 5.7 Hz, 2H), 3.42 (q, J = 5.7 Hz, 2H), 3.78(d, J = 5.7 Hz, 2H), 419 (s, 2H), 4.68 (t, t = 5.7 Hz, 1H), 7.43-7.59(m, 2H), 7.50- 7.53 (m, 3H), 7.97 (t, J = 5.7 Hz, 1H), 8.11-8.19 (m,3H), 8.40 (d, J = 5.7 Hz, 1H), 8.64 (t, J = 5.7 Hz, 1H). II-2-167

(DMSO-d6) δ: 2.91 (s, 3H), 3.00 (q, J = 6.3 Hz, 2H), 3.20 (q, J = 6.3Hz, 2H), 3.78 (d, J = 5.7 Hz, 2H), 419 (s, 2H), 7.06 (t, J = 6.0 Hz,1H), 8.13-8.19 (m, 3H), 8.41 (d, J= 8.4 Hz, 1H), 8.67 (t, J = 5.7 Hz,1H). II-2-168

(DMSO-d6) δ: 2.90 (s, 3H), 3.00 (q, J = 5.7 Hz, 2H), 3.76 (q, J = 5.7Hz, 2H), 3.76 (d, J = 5.7 Hz, 2H), 3.84 (s, 2H), 4.12 (s, 1H), 7.05 (t,J = Hz, 1H), 7.32-7.37 (m, 3H), 7.40-7.45 (m, 2H), 7.62 (s, 1H), 7.94(s, 1H), 8.05 (t, J = 5.7 Hz, 1H), 8.60 (t, J = 5.7 Hz, 1H). II-2-169

1H-NMR (DMSO-d6) δ: 3.86 (d, J = 5.6 Hz, 2H), 4.16 (s, 2H), 4.60 (d, J =5.6 Hz, 2H), 7.39 (t, J = 7.6 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.77(td, J = 9.1, 3.5 Hz, 3H), 8.01 (d, J = 8.6 Hz, 1H), 8.38 (d, J = 1.5Hz, 1H), 8.66 (t, J = 5.6 Hz, 1H), 8.74 (t, J = 5.6 Hz, 1H). II-2-170

(DMSO-d6) δ: 3.84 (d, J = 5.4 Hz, 2H), 4.11 (s, 2H), 7.26 (s, 1H),7.39-7.51 (m, 3H), 7.77 (d, J = 7.2 Hz, 2H). 7.90 (s, 1H), 8.69 (m, 1H),12.67 (br-s, 1H)

TABLE 84 retention No. Structure NMR(δ) time Mass method II-2-171

(DMSO-d₆) δ: 3.85 (d, J = 5.58 Hz, 2H), 4.16 (s, 2H), 7.39 (m, 1H),7.47-7.53 (m, 2H), 7.71-7.79 (m, 3H), 8.14 (d, J = 8.11 Hz, 1H), 8.21(br s, 1H), 8.71 (t, J = 5.58 Hz, 1H), 12.64 (brs, 1H). II-2-172

(DMSO-d₆) δ: 3.83 (d, J = 5.58 Hz, 2H), 4.15-4.19 (m, 4.0H), 7.40 (m,1H), 7.47- 7.53 (m, 2H), 7.72-7.79 (m, 3H), 8.14 (d, J = 8.11 Hz, 1H),8.21 (d, J = 1.01 Hz, 1H), 8.69 (t, J = 5.32 Hz, 1H), 8.74 (t, J = 5.83Hz, 1H). II-2-173

(DMSO-d6) δ: 3.83 (d, J = 6.1 Hz, 2H), 4.02 (s, 2H), 4.19 (d, J= 5.6 Hz,2H), 7.38 (t. J = 6.8 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 7.66-7.73 (m,3H), 7.78 (d, J = 8.1 Hz, 1H), 7.98 (s, 1H), 8.71 (q, J = 5.2 Hz, 2H).II-2-174

(DMSO-d6) δ: 3.84 (d, J = 5.7 Hz, 2H), 4.17 (d, J = 5.7 Hz, 2H), 4.23(s, 2H), 8.71- 8.61 (m, 2H), 8.79 (t, J = 5.7 Hz., 1H), 8.90 (d, J = 2.1Hz, 1H). II-2-175

(DMSO-d6) δ: 3.86 (d, J = 5.7 Hz, 2H), 4.19 (d, J = 5.7 Hz, 2H), 4.24(s, 2H), 7.42- 7.18 (m, 1H), 7.54-7.57 (m, 2H), 7.80-7.63 (m, 2H),8.75-8.82 (m, 2H), 8.86 (d, J= 2.4 Hz, 1H), 8.86 (d, J = 2.4 Hz., 1H),8.98 (d, J = 2.4 Hz, 1H).

TABLE 85 retention No. Structure NMR(δ) time Mass method II-2-176

1H-NMR (DMSO-d6) δ: 4.17 (s, 2H), 4.62-4.63 (m, 4H), 7.38-7.40 (m, 1H),7.49-7.51 (m, 2H), 7.75- 7.80 (m, 3H), 8.02 (d, J = 8.1 Hz, 1H), 8.38(d, J = 1.5 Hz, 1H), 9.17 (t, J = 5.8 Hz, 1H). II-2-177

(DMSO-d6) δ: 0.85 (t, J = 6.8 Hz, 6H), 2.87 (q, J = 7.1 Hz, 4H), 3.16(q, J = 5.9 Hz, 2H), 3.41 (q, J = 5.7 Hz, 2H), 3.76 (d, J = 6.1 Hz, 2H),4.10 (s, 2H), 4.68 (t, J = 5.6 Hz, 1H), 7.32 (t, J = 6.8 Hz, 1H), 7.42(t, J = 7.6 Hz, 2H), 7.56 (d, J = 8.1 Hz, 2H), 7.63 (s, 1H), 7.82 (s,1H), 7.96 (t, J = 5.1 Hz, 1H), 8.57 (t, J = 5.3 Hz, 1H). II-2-178

(DMSO-d6) δ: 0.85 (t, J = 6.3 Hz, 6H), 2.87 (q, J = 6.8 Hz, 4H), 3.82(d, J = 5.1 Hz, 2H). 4.11 (s, 2H), 4.17 (d, J = 4.6 Hz, 2H), 7.30- 7.44(m, 3H), 7.55-7.64 (m, 6H), 7.84 (s, 1H), 8.67-8.71 (m, 2H). II-2-179

1H-NMR (DMSO-d6) δ: 3.23-3.28 (m, 4H), 4.08 (s, 2H), 7.38-7.40 (m, 1H),7.48-7.51 (m, 2H), 7.76- 7.79 (m, 3H), 8.01 (d, J = 8.6 Hz, 1H), 8.38(d, J = 2.0 Hz, 1H), 8.52-8.53 (m, 1H), 9.52 (s, 1H). II-2-180

1H-NMR (DMSO-d6) δ: 3.73 (s, 3H), 3.94 (d, J = 6.1 Hz, 2H), 4.17 (s,2H), 6.43 (d, J = 2.0 Hz, 1H), 7.37-7.41 (m, 1H), 7.49- 7.53 (m, 3H),7.76-7.79 (m, 3H), 8.05 (d, J = 8.6 Hz, 1H), 8.38 (d, J = 1.5 Hz, 1H),8.69 (t, J = 5.6 Hz, 1H), 10.42 (s, 1H).

TABLE 86 retention No. Structure NMR(δ) time Mass method II-2-181

(DMSO-d6) δ: 4.24 (s, 2H), 4.44 (d, J = 5.7 Hz, 2H), 7.44-7.54 (m, 5H),8.61 (d, J = 2.1 Hz, 1H), 8.99 (t, J = 5.7 Hz., 1H), 1296 (brs, 1H).II-2-182

1H-NMR (DMSO-d6) δ: 2.45 (s, 2H), 4.03-4.05 (m, 2H), 4.18 (s, 2H), 7.39(t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.75-7.81 (m, 3H), 8.02(d, J = 8.6 Hz, 1H), 8.39 (d, J = 1.5 Hz, 1H), 8.80 (t, J = 5.6 Hz, 1H),11.63-11.66 (m, 1H). II-2-183

(DMSO-d₆) δ: 3.60 (s, 3H), 3.70 (d, J = 5.07 Hz, 4.16 (s, 2H), 7.23 (m,1H), 7.50-7.64 (m, 3H), 7.84 (dd, J = 8.62. 1.01 Hz, 1H), 8.01 (d, J =8.62 Hz, 1H), 8.45 (d, J = 1.01 Hz, 1H), 8.69 (t, J = 5.07 Hz, 1H),11.25 (s, 1H). II-2-184

1H-NMR (DMSO-d6) δ: 1.32 (t, J = 7.1 Hz, 3H), 4.19 (s, 2H), 4.41 (q, J =7.1 Hz, 2H ), 4.69 6.1 Hz, 2H), 7.39 (t, J = 7.4 Hz, 1H). 7.48-7.51 (m,2H), 7.74-7.81 (m, 3H), 8.01 (d, J = 8.6 Hz, 1H), 8.39 (d, J = 2.0 Hz,1H), 9.24 (t, J = 5.6 Hz, 1H). II-2-185

(DMSO-d6) δ: 3.82 (d, J = 5.6 Hz, 2H), 4.10 (s, 2H), 4.16 (d, J = 5.6Hz, 2H), 6.60 (td, J = 8.4, 2.2 Hz, 1H), 6.83 (d, J = 11.7 Hz, 1H), 6.91(dd, J = 8.1, 1.0 Hz, 1H), 7.18-7.28 (m, 2H), 7.64 (d, J = 1.5 Hz, 1H),7.92 (d, J = 8.6 Hz, 1H), 8.58 (s, 1H), 8.66-8.71 (m, 2H).

TABLE 87 retention No. Structure NMR(δ) time Mass method II-2-186

1H-NMR (DMSO-d6) δ: 4.19 (s, 2H), 4.66 ( d, J = 6.1 Hz, 2H), 7.39 (t, J= 7.4 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.76-7.79 (m, 3H), 8.02 (d, J =8.1 Hz, 1H), 8.21 (s, 1H), 8.38 (d, J = 1.5 Hz, 1H), 8.61 (s, 1H), 9.20(t, J= 5.6 Hz, 1H). II-2-187

1H-NMR (DMSO-d6) δ: 4.18-4.21 (m, 2H), 4.73- 4.74 (m, 2H), 7.41-7.50 (m,3H), 7.74-7.81 (m, 3H), 8.01-8.02 (m, 1H), 8.39 (s, 1H), 9.24-9.25 (m,1H). II-2-188

(CDCl3) δ: 3.40 (s, 3H), 4.07 (m, 4H), 4.14 (d, J = 6.1 Hz, 2H),7.07-7.14 (m, 4H), 7.32-7.37 (m, 2H), 7.51 (d, J = 2.0 Hz, 1H), 7.56 (s,1H), 7.65 (d, J = 8.6 Hz, 1H), 7.82 (s, 1H). II-2-189

(CDCl3) δ: 2.99 (s, 3H), 4.12-4.14 (m, 4H), 4.26 (d, J = 5.6 Hz, 2H),6.57 (s, 1H), 7.37 (d, J = 7.6 Hz, 2H), 7.49-7.64 (m, 5H), 7.76 (s, 1H),8.28 (s, 1H). II-2-190

(DMSO-d₆) δ: 3.83 (d, J = 5.58 Hz, 2H), 4.03 (s, 2H), 4.18 (d, J = 5.58Hz, 2H), 7.39 (m, 1H), 7.46-7.52 (m, 2H), 7.66-7.80 (m, 4H), 8.01 (s,1H), 8.68-8.73 (m, 2H).

TABLE 88 retention No. Structure NMR(δ) time Mass method II-2-191

1H-NMR (DMSO-d6) δ: 4.16 (s, 2H), 4.46 (d, J = 5.1 Hz, 2H), 7.38-7.40(m, 1H), 7.50 ( t, J = 7.6 Hz, 2H), 7.69-7.81 (m, 4H), 8.00-8.03 (m,2H), 8.39 (s, 1H), 8.97 (s, 1H). II-2-192

(DMSO-d6) δ: 3.83 (d, J = 5.7 Hz, 2H), 4.15 (d, J = 5.7 Hz, 2H), 4.17(s, 2H), 7.38-7.52 (m, 6H), 7.62- 7.82 (m, 5H), 8.39 (d, J = 1.5 Hz,1H), 8.68 (t, J = 5.7 Hz, 1H), 8.71 (t, J = 5.7 Hz, 1H). II-2-193

(DMSO-d6) δ: 2.89 (s, 3H), 2.98 (q, J = 5.7 Hz, 2H), 3.76 (d, J = 5.7Hz, 2H), 4.16 (s, 2H), 7.05 (t, J = 5.7 Hz, 6H), 7.81-7.92 (m, 5H), 2H),8.04 (t, J = 5.7 Hz., 1H), 8.38 (d, J = 1.8 Hz, 1H), 8.60 (t, J= 5.7 Hz,1H). II-2-194

1H-NMR (DMSO-d6) δ: 4.21-4.22 (m, 4H), 7.38- 7.40 (m, 1H), 7.48-7.51 (m,2H), 7.76-7.80 (m, 3H), 8.03 (d, J = 8.6 Hz, 1H), 8.39 (d, J = 1.5 Hz,1H), 8.93 (t, J = 5.6 Hz, 1H), 13.42 (s, 1H). II-2-195

(DMSO-d6) δ: 3.83 (d, J = 5.6 Hz, 2H), 4.13 (s, 2H), 7.30-7.40 (m, 6H),7.86 (d, J = 1.0 Hz, 1H), 8.09 (d, J = 8.6 Hz, 1H), 8.70 (t, J = 5.6 Hz,1H).

TABLE 89 retention No. Structure NMR(δ) time Mass method II-2-196

(DMSO-d6) δ: 3.81 (d, J = 6.1 Hz, 2H), 4.14-4.16 (m, 4H), 7.32-7.41 (m,6H), 7.87 (s, 1H), 8.09 (d, J = 8.6 Hz, 1H), 8.67 (t, J = 5.3 Hz, 1H),8.72 (t, J = 5.8 Hz, 1H). II-2-197

1H-NMR (DMSO-d6) δ: 4.18 (s, 2H), 4.53 (d, J = 5.6 Hz, 2H), 7.39-7.52(m, 3H), 7.76-7.80 (m, 3H), 8.02 (d, J = 8.6 Hz, 1H), 8.39 (d, J = 1.5Hz, 1H), 9.11 (t, J= 5.6 Hz, 1H), 15.16 (s, 1H). II-2-198

1H-NMR (DMSO-d6) δ: 3.71 (d, J= 5.6 Hz, 2H), 4.13 (s, 2H), 7.37-7.40 (m,1H), 7.49 (t, J = 7.6 Hz, 2H), 7.75-7.79 (m, 3H), 8.01 (d, J = 8.6 Hz,1H), 8.37-8.37 (m, 2H). II-2-199

(DMSO-d₆) δ: 2.38 (t, J = 7.10 Hz, 2H), 3.34 (dt, J = 7.10, 5.32 Hz,2H),8.64 (t, J = 5.58, Hz, 1.0H), 4.05 (s, 2H), 7.22 (m, 1.0H), 7.50-7.64 (m, 3H), 7.83 (dd, J = 8.36, 1.77 Hz, 1H), 8.01 (d, J = 8.11 Hz,1H), 8.43 (d, J = 1.01 Hz, 1H), 8.48 (t, J = 5.32 Hz, 1H). II-2-200

(DMSO-d6) δ: 3.84 (d, J = 5.7 Hz, 2H), 4.16-4.18 (m, 4H), 6.59 (s, 1H),7.79 (d, J = 2.1 Hz, 1H), 7.97 (dd, J = 8.4, 2.1 Hz, 1H), 8.18 (d, J =8.7Hz, 1H), 8.40 (d, J = 2.4 Hz, 1H), 8.63 (d, J = 2.7 Hz, 1H),8.67-8.78 (m, 2H)

TABLE 90 retention No. Structure NMR(δ) time Mass method II-2-201

(DMSO-d₆) δ: 1.21-1.70 (m, 8H), 2.13-2.21 (m, 2H), 3.85 (d, J = 5.58 Hz,2H), 4.19 (s, 2H), 7.78-7.87 (m, 3H), 8.01 (d, J = 8.11 Hz, 2H), 8.20(dd, J = 8.62, 1.52 Hz, 1H), 8.31 (d, J = 1.52 Hz, 1H), 8.40 (s, 1H),8.66 (t, J = 5.58 Hz, 1H). II-2-202

(DMSO-d₆) δ: 1.12 (dd, J = 8.11, 5.58 Hz, 2H), 1.49 (dd, J = 8.11, 5.58Hz, 2H), 3.78 (d, J = 5.58 Hz, 2H), 4.16 (s, 2H), 7.40 (m, 1H),7.48-7.53 (m, 2H), 7.71- 7.79 (m, 3H), 8.14 (d, J = 8.11 Hz, 1H), 8.21(d, J = 1.01 Hz, 1H), 8.68 (t, J = 5.58 Hz, 1H), 8.92 (s, 1H). II-2-203

(DMSO-d6) δ: 3.30 (s, 3H), 3.81 (d, J = 5.6 Hz, 2H), 4.08 (s, 2H), 4.16(d, J = 5.6 Hz, 2H), 7.00 (dd, J = 8.6, 2.0 Hz, 1H), 7.09-7.18 (m, 4H),7.43 (d, J = 2.0 Hz, 1H), 7.86 (d, J = 8.6 Hz, 1H), 8.65-8.70 (m, 2H).II-2-204

(DMSO-d₆) δ: 4.18 (s, 2H), 4.24 (d, J = 5.07 Hz, 2H), 7.22 (m, 1H),7.51- 7.64 (m, 3H), 7.85 (dd, J = 8.36, 1.52 Hz, 1H), 8.03 (d, J = 8.36Hz, 1 H), 8.47 (d, J = 1.52 Hz, 1H), 9.09 (t, J = 5.07 Hz, 1H) II-2-205

(DMSO-d6) δ: 3.14 (q, J = 5.7 Hz, 2H), 3.29 (s, 3H), 3.40 (q, J = 5.4Hz, 2H), 3.75 (d, J = 5.6 Hz, 2H), 4.07 (s, 2H), 4.67 (t, J = 5.3 Hz,1H), 6.99 (dd, J = 8.9, 2.3 Hz, 1H), 7.09-7.18 (m, 4H), 7.44 (d, J = 2.0Hz, 1H), 7.85 (d, J = 8.6 Hz, 1H), 7.95 (t, J = 5.1 Hz, 1H), 8.56 (t, J= 5.8 Hz, 1H).

TABLE 91 retention me- No. Structure NMR (δ) time Mass thod II-2-206

(DMSO-d₆) δ: 4.06 (d, J = 5.58 Hz, 2H), 4.17 (s, 2.0H), 5.03 (s, 2.0H),7.37-7.52 (m, 3H), 7.74-7.81 (m, 3H), 8.02 (d, J = 8.62 Hz, 1H), 8.38(d, J = 1.01 Hz, 1H), 8.92 (t, J = 5.83 Hz, 1H). II-2-207

(DMSO-d₆) δ: 1.12 (dd, J = 8.36, 5.32 Hz, 1.49 (dd, J = 8.36, 5.32 Hz,2H), 3.78 (d, J = 6.08 Hz, 2H), 4.16 (s, 2H), 7.22 (m, 1H), 7.50-7.64(m, 3H), 7.84 (dd, J = 8.62, 1.52 Hz, 1H), 8.02 (d, J = 8.11 Hz, 1H),8.45 (d, J = 1.52 Hz, 1H), 8.68 (t, J = 6.08 Hz, 1H), 8.91 (s, 1H).II-2-208

(DMSO-d₆) δ: 1.21-1.70 (m, 8H), 2.14-2.21 (m, 2H), 3.85 (d, J = 6.08 Hz,2H), 4.17 (s, 2H), 7.22 (m, 1H), 7.50-7.64 (m, 3H), 7.84 (dd, J = 8.62,2.03 Hz, 1H), 8.02 (d, J = 8.62 Hz, 1H), 8.40 (s, 1H), 8.45 (d, J = 2.03Hz, 1H), 8.65 (t, J = 5.58 Hz, 1H). II-2-209

(DMSO-d₆) δ: 3.71 (d, J = 5.07 Hz, 2H), 3.99 (t, J = 2.54 Hz, 1H), 4.06(t, J = 2.54 Hz, 1H), 4.15 (s, 2H), 4.54 (t, J = 2.54 Hz, 1H), 4.66 (t,J = 2.54 Hz, 1H), 7.22 (m, 1H), 7.50-7.65 (m, 3H), 7.83 (dd, J = 8.62,1.52 Hz, 1H), 8.02 (d, J = 8.62 Hz, 1H), 8.45 (d, J = 1.52 Hz, 1H), 8.69(t, J = 5.07 Hz, 1H), 11.36 (s, 1.0H). II-2-210

(DMSO-d₆) δ: 3.90 (d, J = 5.07 Hz, 2H), 4.18 (s, 2H), 7.00-7.07 (m, 3H),7.19-7.35 (m, 3H), 7.50-7.64 (m, 3H), 7.83 (dd, J = 8.62, 2.03 Hz, 1H),8.00 (d, J = 8.62 Hz, 1H), 8.46 (d, J = 2.03 Hz, 1H), 8.84 (t, J = 5.07Hz, 1H), 12.01 (s, 1H).

TABLE 92 retention me- No. Structure NMR (δ) time Mass thod II-2-211

(DMSO-d₆) δ: 3.13 (s, 1H), 3.79 (d, J = 5.6 Hz, 2H), 3.90 (m, 2H), 4.16(s, 2H), 7.36-7.42 (m, 1H), 7.46-7.52 (m, 2H), 7.72-7.82 (m, 3H), 8.02(d, J = 8.4 Hz, 1H), 8.38 (s, 1H), 8.40-8.48 (m, 1H), 8.65-8.70 (m, 1H).II-2-212

(DMSO-d₆) δ: 3.91 (d, J = 5.2 Hz, 2H), 4.19 (s, 2H), 4.60 (d, J = 5.6Hz, 2H), 7.36-7.44 (m, 1H), 7.47-7.53 (m, 2H), 7.72-7.80 (m, 3H), 7.90(d, J = 5.2 Hz, 1H), 8.00 (d, J = 8.4 Hz, 1H), 8.39 (s, 1H), 8.78-8.89(m, 4H). II-2-213

(DMSO-d₆) δ: 3.72-3.80 (m, 5H), 4.10-4.18 (m, 4H), 7.31 (s, 1H),7.37-7.43 (m, 1H), 7.46-7.57 (m, 3H), 7.72-7.82 (m, 3H), 7.97-8.02 (m,1H), 8.23-8.28 (m, 1H), 8.38 (s, 1H), 8.61-8 8.67 (m, 1H). II-2-214

2.16 415.95 (ES+) C II-2-215

(DMSO-d₆) δ: 1.05-1.18 (m, 2H), 1.48-1.68 (m, 3H), 2.96-3.02 (m, 2H),3.21 (t, J = 11.2 Hz, 2H), 3.74-3.85 (m, 4H), 4.16 (s, 1H), 7.36-7.42(m, 1H), 7.47-7.54 (m, 2H), 7.72-7.82 (m, 3H), 7.91-7.97 (m, 1H),7.98-8.04 (m, 1H).

TABLE 93 retention me- No. Structure NMR (δ) time Mass thod II-2-216

1.29 439.05 (ES+) C II-2-217

(DMSO-d₆) δ: 4.00 (d, J = 5.2 Hz, 2H), 4.21 (s, 2H), 7.02-7.08 (m, 1H),7.28-7.35 (m, 2H), 7.35-7.42 (m, 1H), 7.46-7.53 (m, 2H), 7.59 (d, J =7.6 Hz, 2H), 7.72-7.82 (m, 3H), 8.02 (d, J = 8.4 Hz, 1H), 8.39 (s, 1H),8.73-8.79 (m, 1H), 10.05 (s, 1H). II-2-218

(DMSO-d₆) δ: 4.06 (d, J = 4.4 Hz, 2H), 4.21 (s, 2H), 7.37-7.43 (m, 1H),7.47-7.53 (m, 2H), 7.73-7.82 (m, 3H), 8.02 (d, J = 7.6 Hz, 1H), 8.39 (s,1H), 8.81-8.87 (m, 1H), 8.91 (s, 1H), 9.00 (s, 2H), 10.51 (s, 1H).II-2-219

(DMSO-d6) δ: 3.43 (d, J = 5.7 Hz, 2H), 4.17 (s, J = 5.7 Hz, 2H), 4.22(s, 2H), 7.38-7.53 (m, 3H), 7.69 (d J = 13.2 Hz, 1H), 7.78 (d, J = 7.2Hz, 2H), 8.26 (d, J = 0.9 Hz, 1H), 8.63 (t, J = 5.4 Hz, 1H), 8.67 (t, J= 5.4 Hz, 1H). II-2-220

(DMSO-d6) δ: 3.16 (q, J = 5.7 Hz, 2H), 3.10 (q, J = 5.7 Hz, 2H), 3.78(d, J = 5.7 Hz, 2H), 4.20 (s, 2H), 4.67 (t, J = 5.7 Hz, 1H), 741 (t, J =5.7 Hz, 1H), 7.51 (t, J = 5.7 Hz, 2H), 7.67 (d, J = 12.0 Hz, 1H), 7.86(d, J = 8.6 Hz, 2H), 7.95 (t, J = 1.8 Hz, 1H), 8.26 (d, J = 0.9 Hz, 1H),8.63 (t, J = 5.7 Hz, 1H).

TABLE 94 retention me- No. Structure NMR (δ) time Mass thod II-2-221

(DMSO-d₆) δ: 3.83 (s, 2H), 4.05 (s, 2H), 4.17 (s, 2H), 7.50-7.58 (m,2H), 7.84 (dd, J = 8.62, 1.52 Hz, 1H), 7.91-8.00 (m, 3H), 8.17 (brs,1H), 8.24 (s, 1H), 8.72 (brs, 2H). II-2-222

(DMSO-d₆) δ: 3.85 (d, J = 6.08 Hz, 2H), 4.16 (s, 2H), 7.22 (m, 1H), 7.53(m, 1H), 7.61-7.66 (m, 2H), 7.77 (dd, J = 8.62, 1.52 Hz, 1H), 8.16 (d, J= 8.62 Hz, 1H), 8.27 (d, J = 1.52 Hz, 1H), 8.71 (t, J = 5.83 Hz, 1H),12.64 (s, 1H). II-2-223

(DMSO-d6) δ: 0.93 (t, J = 7.4 Hz, 3H), 1.62-1.64 (m, 2H), 3.74 (t, J =7.6 Hz, 2H), 3.84 (d, J = 5.9 Hz, 2H), 4.11 (s, 2H), 4.18 (d, J = 5.7Hz, 2H), 6.90-7.04 (m, 3H), 7.09 (dd, J = 8.6, 2.3 Hz, 1H), 7.29 (t, J =8.0 Hz, 2H), 7.53 (d, J = 2.4 Hz, 1H), 7.91 (d, J = 8.7 Hz, 1H),8.63-8.74 (m, 2H). II-2-224

(CDCl3) δ: 3.03 (s, 6H), 3.76 (s, 2H), 4.08-4.15 (m, 4H), 6.80 (dd, J =9.0, 2.4 Hz, 1H), 6.97-7.01 (m, 3H), 7.34 (t, J = 7.2 Hz, 1H), 7.74 (d,J = 15 Hz, 1H), 7.81 (br-s, 1H), 8.03-8.06 (m, 2H). II-2-225

(DMSO-d₆) δ: 3.83 (d, J = 5.58 Hz, 2H), 4.16-4.19 (m, 4H), 7.23 (m, 1H),7.50-7.66 (m, 3H), 7.77 (dd, J = 8.62, 1.52 Hz, 1H), 8.16 (d, J = 8.62Hz, 1H), 8.27 (d, J = 1.52 Hz, 1H), 8.69 (t, J = 5.58 Hz, 1H), 8.74 (t,J = 5.58 Hz, 1H).

TABLE 95 retention No. Structure NMR (δ) time Mass method II-2-226

(DMSO-d₆) δ: 1.12 (dd, J = 8.11, 5.83 Hz, 2H), 1.49 (dd, J = 8.11, 5.58Hz, 2H), 3.78 (d, J = 5.83 Hz, 2H), 4.17 (s, 2H), 7.23 (m, 1H),7.51-7.66 (m, 3H), 7.77 (dd, J = 8.36, 1.52 Hz, 1H), 8.16 (d, J = 8.36Hz, 1H), 8.27 (d, J = 1.52 Hz, 1H), 8.69 (t, J = 5.83 Hz, 1H), 8.92 (s,1H). II-2-227

(DMSO-d₆) δ: 3.85 (d, J = 5.58 Hz, 2H), 4.16 (s, 2.0H), 7.32 (t, J =8.61 Hz, 2H), 7.71 (dd, J = 8.11, 1.52 Hz, 1H), 7.79-7.84 (m, 2H), 8.14(d, J = 8.11 Hz, 1H), 8.20 (d, J = 1.52 Hz, 1H), 8.71 (t, J = 5.83 Hz,1H), 12.64 (s, 1H). II-2-228

(DMSO-d₆) δ: 3.83 (d, J = 5.58 Hz, 2H), 4.15-4.19 (m, 4H), 7.33 (t, J =8.87 Hz, 2H), 7.71 (dd, J = 8.62, 1.52 Hz, 1H), 7.79-7.84 (m, 2H), 8.14(d, J = 8.62 Hz, 1H), 8.20 (d, J = 1.52 Hz, 1H), 8.69 (t, J = 5.58 Hz,1H), 8.73 (t, J = 5.83 Hz, 1H). II-2-229

(DMSO-d₆) δ: 1.12 (dd, J = 8.36, 5.32 Hz, 2H), 1.49 (dd, J = 8.36. 5.32Hz, 2H), 3.77 (d, J = 5.58 Hz, 2H), 4.16 (s, 2H), 7.29-7.35 (m, 2H),7.71 (dd, J = 8.62, 1.52 Hz, 1H), 7.79-7.84 (m, 2H), 8.14 (d, J = 8.62Hz, 1H), 8.20 (d, J = 1.52 Hz, 1H), 8.68 (t, J = 5.58 Hz, 1H), 8.91 (s,1H). II-2-230

(DMSO-d₆) δ: 3.85 (d, J = 5.58 Hz, 2H), 4.17 (s, 2H), 7.71-7.83 (m, 3H),8.07-8.12 (m, 2H), 8.19 (d, J = 8.11 Hz, 1H), 8.32 (d, J = 1.52 Hz, 1H),8.72 (t, J = 5.83 Hz, 1H).

TABLE 96 retention me- No. Structure NMR (δ) time Mass thod II-2-231

(DMSO-d₆) δ: 3.84 (d, J = 6.08 Hz, 2H), 4.16-4.20 (m, 4H), 7.71-7.84 (m,3H), 8.07-8.12 (m, 2H), 8.19 (d, J = 8.62 Hz, 1H), 8.32 (d, J = 1.52 Hz,1H), 8.69 (t, J = 5.58 Hz, 1H), 8.74 (t, J = 5.83 Hz, 1H). II-2-232

(DMSO-d₆) δ: 1.13 (dd, J = 8.11, 5.58 Hz, 2H), 1.49 (dd, J = 8.11, 5.58Hz, 2 H), 3.78 (d, J = 6.08 Hz, 2H), 4.18 (s, 2H), 7.71-7.84 (m, 3H),8.06-8.12 (m, 2H), 8.19 (d, J = 8.62 Hz, 1H), 8.32 (d, J = 1.52 Hz, 1H),8.69 (t, J = 5.58 Hz, 1H), 8.92 (s, 1H). II-2-233

(DMSO-d₆) δ: 3.13 (t, J = 2.53 Hz, 1H), 3.78 (d, J = 6.08 Hz, 2H), 3.90(dd, J = 5.58, 2.53 Hz, 2H), 4.16 (s, 2H), 7.40 (t, J = 7.35 Hz, 1H),7.47-7.53 (m, 2H), 7.73 (dd, J = 8.62, 1.52 Hz, 1H), 7.77 (d, J = 7.10Hz, 2H), 8.14 (d, J = 8.62 Hz, 1H), 8.22 (d, J = 1.52 Hz, 1H), 8.44 (t,J = 5.32 Hz, 1H), 8.67 (t, J = 5.83 Hz, 1H). II-2-234

(DMSO-d₆) δ: 3.12 (t, J = 2.53 Hz, 1H), 3.78 (d, J = 5.58 Hz, 2H), 3.90(dd, J = 5.58, 2.53 Hz, 2H), 4.16 (s, 2H), 7.22 (m, 1H), 7.50-7.64 (m,3H), 7.84 (dd, J = 8.62, 1.77 Hz, 1H), 8.02 (d, J = 8.62 Hz, 1H),8.40-8.46 (m, 2H), 8.67 (t, J = 5.83 Hz, 1H). II-2-235

(DMSO-d6) δ: 3.83-3.87 (m, 5H), 4.15 (s, 2H), 6.96 (m, 1H), 7.26-7.35(m, 2H), 7.41 (t, J = 8.0 Hz, 1H), 7.80 (dd, J = 8.6, 1.8 Hz, 1H), 8.00(d, J = 8.6 Hz, 1H), 8.40 (d, J = 1.5 Hz, 1H), 8.71 (t, J = 6.1 Hz, 1H).

TABLE 97 retention me- No. Structure NMR (δ) time Mass thod II-2-236

(DMSO-d6) δ: 3.81-3.86 (m, 5H), 4.15-4.19 (m, 4H), 6.96 (dd, J = 8.1,2.5 Hz, 1H), 7.27-7.34 (m, 2H), 7.41 (t, J = 7.8 Hz, 1H), 7.80 (dd, J =8.5, 1.9 Hz, 1H), 8.01 (d, J = 8.6 Hz, 1H), 8.40 (d, J = 1.8 Hz, 1H),8.65-8.77 (m, 2H). II-2-237

(DMSO-d6) δ: 3.85 (d, J = 5.7 Hz, 2H), 4.16 (s, 2H), 7.46 (m, 1H), 7.53(t, J = 7.8 Hz, 1H), 7.72-7.76 (m, 1H), 7.81-7.85 (m, 2H), 8.02 (d, J =8.4 Hz, 1H), 8.45 (d, J = 1.5 Hz, 1H), 8.72 (t, J = 5.8 Hz, 1H).II-2-238

(DMSO-d₆) δ: 2.88 (s, 1H), 3.01 (s, 2H), 4.02-4.23 (m, 6H), 7.36-7.42(m, 1H), 7.46-7.53 (m, 2H), 7.72-7.82 (m, 3H), 8.02 (d, J = 8.4 Hz, 1H),8.38 (s, 1H), 8.53-8.59 (m, 1H). II-2-239

(DMSO-d₆) δ: 3.93 (d, J = 5.2 Hz, 2H), 4.30 (s, 2H), 7.11-7.18 (m, 1H),7.35-7.43 (m, 1H), 7.46-7.56 (m, 3H), 7.72-7.87 (m, 5H), 8.03 (d, J =8.4 Hz, 1H), 8.31-8.35 (m, 1H), 8.38 (m, 1H), 8.56 (d, J = 8.4 Hz, 1H),9.09-9.13 (m, 1H), 12.21 (s, 1H). II-2-240

(DMSO-d₆) δ: 4.01 (d, J = 4.8 Hz, 2H), 4.21 (s, 2H), 7.32-7.43 (m, 3H),7.45-7.59 (m, 3H), 7.72-7.83 (m, 5H), 7.93-7.97 (m, 1H), 7.99-8.07 (m,2H), 8.39 (s, 1H), 8.75-8.82 (m, 1H), 10.17 (s, 1H).

TABLE 98 reten- tion No. Structure NMR(δ) time Mass method II-2-241

(DMSO-d₆) δ: 4.01 (d, J = 5.2 Hz, 2 H), 4.20 (s, 2 H), 7.22-7.28 (m, 1H), 7.37- 7.43 (m, 1 H), 7.45-7.54 (m, 2 H), 7.65 (d, J = 8.4 Hz, 2 H),7.72-7.88 (m, 6 H), 8.02 (d, 8.4 Hz, 1 H), 8.39 (s, 1 H), 8.75-8.82 (m,1 H), 10.27 (s, 1 H). II-2-242

(DMSO-d₆) δ: 4.03 (d, J = 4.8 Hz, 2 H), 4.22 (s, 2 H), 7.32-7.54 (m, 8H), 7.56- 7.63 (m, 3 H), 7.72-7.82 (m, 3 H), 7.92 (s, 1 H), 8.02 (d, J =8.8 Hz, 2 H), 8.38 (s, 1 H), 8.75-8.81 (m, 1 H), 10.15 (s, 1 H).II-2-243

(DMSO-d₆) δ: 4.17 (d, J = 3.2 Hz, 2 H), 4.24 (s, 2 H), 7.35-7.43 (m, 1H), 7.45- 7.56 (m, 4 H), 7.64-7.69 (m, 1 H), 7.72-7.82 (m, 3 H), 7.94(d, J = 7.2 Hz, 2 H), 8.05-8.11 (m, 2 H), 8.39 (s, 1 H), 8.84-8.90 (m, 1H), 10.05 (s, 1 H). II-2-244

(DMSO-d₆) δ: 4.03 (d, J = 4.8 Hz, 2 H), 4.21 (s, 2 H), 7.27 (s, 2 H),7.35-7.43 (m, 1 H), 7.45-7.54 (m, 2 H), 7.71-7.83 (m, 7 H), 8.02 (d, J =8.4 Hz, 1 H), 8.39 (s, 1 H), 8.75-8.82 (m, 1 H), 10.40 (s, 1 H).II-2-245

(DMSO-d₆) δ: 3.73 (s, 3 H), 4.00 (d, J = 5.2 Hz, 2 H), 4.21 (s, 2 H),6.64 (d, J = 7.6 Hz, 1 H), 7.13 (d, J = 7.6 Hz, 1 H), 7.18-7.26 (m, 1H), 7.31 (s, 1 H), 7.35-7.42 (m, 1 H), 7.45-7.53 (m, 2 H), 7.72-7.82 (m,3 H), 8.02 (d, J = 8.4 Hz, 1 H), 8.38 (s, 1 H), 8.73-8.79 (m, 1 H),10.04 (s, 1 H).

TABLE 99 reten- tion No. Structure NMR(δ) time Mass method II-2-246

(DMSO-d₆) δ: 3.39 (s, 3 H), 3.97 (d, J = 4.4 Hz, 2 H), 4.20 (s, 2 H),6.89 (d, J = 8.4 Hz, 2 H), 7.36-7.43 (m, 1 H), 7.45-7.53 (m, 4 H),7.72-7.82 (m, 3 H), 8.01 (d, J = 8.4 Hz, 1 H), 8.38 (s, 1 H), 8.71-8.77(m, 1 H), 9.90 (s, 1 H). II-2-247

(DMSO-d₆) δ: 3.17 (s, 3 H), 4.05 (d, J = 4.0 Hz, 2 H), 4.21 (s, 2 H),7.37-7.43 (m, 1 H), 7.46-7.53 (m, 2 H), 7.72-7.90 (m, 7 H), 8.02 (d, J =7.6 Hz, 1 H), 8.39 (s, 1 H), 8.77-8.83 (m, 1 H), 10.51 (s, 1 H).II-2-248

(DMSO-d₆) δ: 4.03 (d, J = 5.2 Hz, 2 H), 4.20 (s, 2 H), 7.36-7.43 (m, 1H), 7.46- 7.53 (m, 2 H), 7.66-7.83 (m, 7 H), 8.02 (d, J = 8.8 Hz, 1 H),8.39 (s, 1 H), 8.76-8.82 (m, 1 H), 10.43 (s, 1 H). II-2-249

(DMSO-d6) δ: 3.83 (d, J = 6.0 Hz, 2 H), 4.16-4.18 (m, 4 H), 6.58 (s, 1H), 7.79 (s, 1 H), 8.00-8.06 (m, 2 H), 8.54-8.57 (m, 2 H), 8.68- 8.74(m, 2 H) II-2-250

(DMSO-d6) δ: 2.98 (s, 6 H), 3.65 (s, 4 H), 3.94 (d, J = 5.4 Hz, 2 H),4.15 (s, 2 H), 6.75 (d, J = 9.6 Hz, 1 H), 6.98-7.01 (m, 2 H), 7.29 (t, J= 7.5 Hz, 1 H), 7.77 (d, J = 8.4 Hz, 1 H), 8.00 (d, J = 9.0 Hz, 1 H ),8.36 (s, 1 H), 8.82 (br-s, 1 H)

TABLE 100 reten- tion No. Structure NMR( δ) time Mass method II-2-251

(DMSO-d₆) δ: 3.83 (d, J = 6.08 Hz, 2 H), 4.18-4.15 (m, 4 H), 7.36 (d, J= 7.60 Hz, 1 H), 7.49 (d, J = 7.60 Hz, 1 H), 7.65 (dd, J = 7.35, 7.60Hz, 1 H), 7.76 (dd, J = 7.35, 7.60 Hz, 1 H), 7.85- 7.89 (m, 2 H), 8.13(d, J = 8.11 Hz, 1 H), 8.68 (t, J = 5.58 Hz, 1 H), 8.74 (t, J = 5.58 Hz,1 H). II-2-252

(DMSO-d6) δ: 3.86 (d, J = 5.7 Hz, 2 H), 4.18 (d, J = 5.4 Hz, 2 H), 4.25(s, 2 H), 7.26- 7.30 (m, 1 H), 7.54-7.64 (m, 1 H), 7.67-7.73 (m, 1 H),8.75-8.81 (m, 1 H), 8.93 (d, J = 2.4 Hz, 2 H), 9.02 (d, J = 2.41 Hz, 1H). II-2-253

(DMSO-d6) δ: 3.86 (d, J = 5.7 Hz, 2 H), 4.19 (d, J = 5.4 Hz, 4 H), 4.25(s, 2 H), 7.34- 7.41 (m, 2 H), 7.85-7.89 (m, 2 H), 8.75-8.82 (m, 2 H),8.86 (d, J = 2.4 Hz, 1 H), 8.962 (d, J = 2.4 Hz, 1 H). II-2-254

(DMSO-d6) δ: 2.26-2.33 (m, 2 H), 2.84 (s, 1 H), 3.18- 3.25 (m, 2 H),3.77 (d, J = 5.2 Hz, 2 H), 4.16 (s, 2 H), 7.36-7.43 (m, 1 H), 7.46- 7.53(m, 2 H), 7.72-7.82 (m, 3 H), 8.02 (d, J = 8.8 Hz, 1 H), 8.12-8.18 (m, 1H), 8.38 (s, 1 H), 8.62-8.68 (m, 1 H). II-2-255

(DMSO-d6) δ: 0.13- 0.19 (m, 2 H), 0.37-0.43 (m, 2 H), 0.86-0.93 (m, 1H), 2.94-3.02 (m, 2 H), 3.77 (d, J = 5.2 Hz, 2 H), 4.16 (s, 2 H),7.36-7.43 (m, 1 H), 7.46-7.53 (m, 2 H), 7.72- 7.82 (m, 3 H), 8.01 (d, J= 8.8 Hz, 2 H), 8.38 (s, 1 H), 8.60-8.66 (m, 1 H).

TABLE 101 reten- tion No. Structure NMR(δ) time Mass method II-2-256

(DMSO-d6) δ: 3.82 (d, J = 6.1 Hz, 2 H), 4.11 (s, 2 H), 4.16 (d, J = 5.6Hz, 2 H), 6.94-6.97 (m, 2 H), 7.16 (dd, J = 8.6, 2.5 Hz, 1 H), 7.27-7.28 (m, 2 H), 7.62 (d, J = 2.5 Hz, 1 H), 7.96 (d, J = 8.6 Hz, 1 H),8.66-8.71 (m, 2 H). 2.1  428.00 (ES+) C II-2-257

(DMSO-d6) δ: 3.14 (q, J = 5.9 Hz, 2 H), 3.40 (q, J = 5.9 Hz, 2 H), 3.75(d, J = 5.6 Hz, 2 H), 4.08 (s, 2 H), 4.67 (t, J = 5.6 Hz, 1 H), 6.96 (t,J = 7.4 Hz, 1 H), 7.03 (d, J = 7.6 Hz, 2 H), 7.09 (dd, J = 8.9, 2.3 Hz,1 H), 7.29 (t, J = 8.1 Hz, 2 H), 7.53 (d, J = 2.0 Hz, 1 H), 7.89 (d, J =8.6 Hz, 1 H), 7.95 (t, J = 5.3 Hz, 1 H), 8.56 (t, J = 5.6 Hz, 1 H). 1.75398.95 (ES+) C II-2-258

(DMSO-d6) δ: 3.84 (d, J = 5.9 Hz, 2 H), 4.15-4.20 (m, 4 H), 7.44-7.47(m, 1 H), 7.53 (t, J = 7.8 Hz, 1 H), 7.74 (dt, J = 7.6, 1.5 Hz, 1 H),7.81-7.85 (m, 2 H), 8.03 (d, J = 8.4 Hz, 1 H), 8.45 (d, J = 1.8 Hz, 1H), 8.65-8.78 (m, 2 H) II-2-259

(DMSO-d6) δ: 3.84 (d, J = 5.9 Hz, 2 H), 4.15-4.20 (m, 4 H), 7.26 (tt, J= 9.3, 2.3 Hz, 1 H), 7.51-7.59 (m, 2 H), 7.88 (dd, J = 8.6, 1.9 Hz, 1H), 8.03 (d, J = 8.6 Hz, 1 H), 8.51 (d, J = 1.8 Hz, 1 H), 8.65-8.78 (m,2 H). II-2-260

(DMSO-d6) δ: 3.85 (d, J = 5.7 Hz, 2 H), 4.16 (s, 2 H), 7.49-7.67 (m, 2H), 7.78- 7.92 (m, 2 H), 8.02 (d, J = 8.6 Hz, 1 H), 8.43 (d, J = 1.7 Hz,1 H), 8.72 (t, J = 5.8 Hz, 1 H).

TABLE 102 reten- tion No. Structure NMR(δ) time Mass method II-2-261

(DMSO-d6) δ: 3.32 (s, 3 H), 3.83 (d, J = 5.7 Hz, 2 H), 4.06 (s, 2 H),6.92-7.06 (m, 2 H), 7.11 (dd, J = 8.9, 2.4 Hz, 1 H), 7.27-7.32 (m, 3 H),7.66 (d, J = 2.2 Hz, 1 H), 7.80 (d, J = 8.9 Hz, 1 H), 8.66 (t, J = 5.5Hz, 1 H). II-2-262

(DMSO-d6) δ: 3.45 (s, 3 H), 3.82 (d, J = 6.1 Hz, 2 H), 4.14-4.18 (m, 4H), 6.55 (d, J = 8.6 Hz, 1 H), 6.69 (dd, J = 7.1, 5.1 Hz, 1 H), 7.35(dd, J = 8.6, 2.0 Hz, 1 H), 7.43 (td, J = 7.9, 1.9 Hz, 1 H), 7.85 (d, J= 2.0, Hz, 1 H), 8.08 (d, J = 8.6 Hz, 1 H), 8.17 (dd, J = 4.8, 1.3 Hz, 1H), 8.66-8.73 (m, 2 H). II-2-263

(DMSO-d6) δ: 3.80 (d, J = 6.0 Hz, 2 H), 3.90 (d, J = 5.4 Hz, 2 H), 4.20(s, 2 H), 7.47- 7/56 (m, 3 H), 8.12-8.18 (m, 3 H), 8.39-8.42 (m, 2 H),8.69 (t, J = 5.4 Hz, 1 H). II-2-264

(DMSO-d₆) δ: 1.12 (dd, J = 8.36, 5.32 Hz, 2 H), 1.49 (dd, J = 8.36, 5.32Hz, 2 H), 3.77 (d, J = 5.58 Hz, 2 H), 4.17 (s, 2 H), 7.36 (d, J = 8.11Hz, 1 H), 7.49 (d, J = 7.60 Hz, 1 H), 7.65 (dd, J = 8.11, 7.60 Hz, 1 H),7.76 (dd, J = 7.60, 8.11 Hz, 1 H), 7.85-7.89 (m, 2 H), 8.13 (d, J = 8.11Hz, 1 H), 8.69 (t, J = 5.58 Hz, 1 H), 8.91 (s, 1 H). II-2-265

(CDCl3) δ: 0.97 (t, J = 7.4 Hz, 3 H), 1.16-1.20 (m, 2 H), 1.42-1.46 (m,2 H), 1.69- 1.78 (m, 2 H), 3.73 (t, J = 7.6 Hz, 2 H), 4.00 (d, J = 6.1Hz, 2 H), 4.06 (s, 2 H), 7.03- 7.11 (m, 4 H), 7.33 (t, J = 8.1 Hz, 2 H),7.53 (s, 1 H), 7.62-7.69 (m, 3 H).

TABLE 103 reten- tion meth- No. Structure NMR(δ) time Mass od II-2-266

(DMSO-d6) δ: 3.82 (d, J = 5.9 Hz, 2 H), 4.08 (s, 2 H), 4.17 (d, J = 5.7Hz, 2 H), 6.93-7.06 (m, 3 H), 7.11 (dd, J = 8.9, 2.4 Hz, 1 H), 7.30 (t,J = 7.9 Hz, 2 H), 7.66 (d, J = 2.4 Hz, 1 H), 7.80 (d, J = 9.1 Hz, 1 H),8.68 (m, 2 H). 1.9 394.00 (ES+) C II-2-267

(DMSO-d6) δ: 1.27-1.34 (m, 3 H), 3.93-4.00 (m, 4 H), 4.20 (s, 2 H), 6.87(d, J = 8.0 Hz, 2 H), 7.36-7.43 (m, 1 H), 7.46-7.53 (m, 4 H), 7.72-7.82(m, 3 H), 8.02 (d, J = 8.4 Hz, 1 H), 8.38 (s, 1 H), 8.71-8.78 (m, 1 H),9.89 (s, 1 H). II-2-268

(DMSO-d6) δ: 3.94 (d, J = 4.8 Hz, 2 H), 4.19 (s, 2 H), 6.71 (d, J = 8.4Hz, 2 H), 7.33-7.43 (m, 3 H), 7.45- 7.53 (m, 2 H), 7.72-7.82 (m, 3 H),8.01 (d, J = 8.0 Hz, 1 H), 8.38 (s, 1 H), 8.70-8.76 (m, 1 H), 9.22 (s, 1H), 9.78 (s, 1 H). II-2-269

(DMSO-d6) δ: 4.01 (d, J = 3.2 Hz, 2 H), 4.20 (s, 2 H), 7.33 (d, J = 8.0Hz, 2 H), 7.36-7.43 (m, 1 H), 7.46- 7.53 (m, 2 H), 7.66-7.82 (m, 5 H),8.02 (d, J = 8.8 Hz, 1 H), 8.38 (s, 1 H), 8.76-8.82 (m, 1 H), 10.27 (s,1 H). II-2-270

(DMSO-d6) δ: 1.23 (d, J = 5.6 Hz, 6 H), 3.96 (d, J = 4.0 Hz, 2 H), 4.20(s, 2 H), 4.48- 4.55 (m, 1 H), 6.86 (d, J = 8.4 Hz, 2 H), 7.36-7.43 (m,1 H), 7.46-7.53 (m, 4 H), 7.72-7.82 (m, 3 H), 8.01 (d, J = 8.4 Hz, 1 H),8.38 (s, 1 H), 8.71-8.78 (m, 1 H), 9.89 (s, 1 H).

TABLE 104 reten- tion meth- No. Structure NMR(δ) time Mass od II-2-271

(DMSO-d6) δ: 1.51-1.92 (m, 8 H), 3.96 (d, J = 5.2 Hz, 2 H), 4.19 (s, 2H), 4.71-4.78 (m, 1 H), 6.85 (d, J = 8.4 Hz, 2 H), 7.36-7.53 (m, 5 H),7.72-7.82 (m, 3 H), 8.01 (d, J = 8.4 Hz, 1 H), 8.39 (s, 1 H), 8.70-8.77(m, 1 H), 9.87 (s, 1 H). II-2-272

(DMSO-d6) δ: 1.50-1.59 (m, 2 H), 1.90-1.98 (m, 2 H), 3.41-3.50 (m, 2 H),3.78- 3.88 (m, 2 H), 3.96 (d, J = 4.8 Hz, 2 H), 4.20 (s, 2 H), 4.44-4.53(m, 1 H), 6.93 (d, J = 8.4 Hz, 2 H), 7.36-7.43 (m, 1 H), 7.45-7.52(m, 4H), 7.72-7.82 (m, 3 H), 8.01 (d, J = 8.4 Hz, 1 H), 8.38 (s, 1 H),8.71-8.78 (m, 1 H), 9.90 (s, 1 H). II-2-273

(DMSO-d6) δ: 3.98 (d, J = 4.8 Hz, 2 H), 4.20 (s, 2 H), 5.13 (s, 2 H),7.04 (d, J = 8.4 Hz, 2 H), 7.36-7.43 (m, 1 H), 7.46-7.52 (m, 2 H),7.52-7.60 (m, 2 H), 7.72- 7.82 (m, 3 H), 8.02 (d, J = 8.0 Hz, 1 H), 8.39(s, 1 H), 8.72-8.79 (m, 1 H), 10.02 (s, 1 H). II-2-274

(DMSO-d6) δ: 4.04 (d, J = 5.2 Hz, 2 H), 4.22 (s, 2 H), 7.36-7.52 (m, 4H), 7.70-7.82 (m, 4 H), 8.02 (d, J = 8.4 Hz, 1 H), 8.22 (s, 1 H), 8.38(s, 1 H), 8.66 (s, 1 H), 8.74-8.83 (m, 1 H), 10.36 (s, 1 H). II-2-275

(DMSO-d6) δ: 4.05 (d, J = 4.8 Hz, 2 H), 4.23 (s, 2 H), 6.77 (d, J = 6.8Hz, 1 H), 7.19-7.29 (m, 2 H), 7.35- 7.43 (m, 1 H), 7.45-7.56 (m, 3 H),7.71-7.82 (m, 3 H), 7.99-8.11 (m, 2 H), 8.18 (s, 1 H), 8.39 (s, 1 H),8.77- 8.83 (m, 1 H), 10.07 (s, 1 H), 10.20 (s, 1 H).

TABLE 105 reten- tion meth- No. Structure NMR(δ) time Mass od II-2-276

(DMSO-d6) δ: 2.02 (s, 3 H), 3.97 (d, J = 4.8 Hz, 2 H), 4.20 (s, 2 H),7.35- 7.45(m, 1 H), 7.47-7.53 (m, 6 H), 7.72-7.82 (m, 3 H), 8.02 (d, J =8.8 Hz, 1 H), 8.38 (s, 1 H), 8.72- 8.78 (m, 1 H), 9.88 (s, 1 H), 9.97(s, 1 H). II-2-277

(DMSO-d₆) δ: 3.81 (d, J = 6.08 Hz, 2 H), 3.98 (s, 2 H), 4.16 (d, J =5.58 Hz, 2 H), 6.94 (d, J = 16.22 Hz, 1 H), 7.28 (m, 1 H), 7.34-7.40 (m,2.0 H), 7.45 (d, J = 16.22 Hz, 1 H), 7.56- 7.59 (m, 2 H), 7.76 (s, 1 H),8.64 (t, J = 5.83 Hz, 1 H), 8.68 (t, J = 5.58 Hz, 1 H). II-2-278

(DMSO-d6) δ: 3.83 (d, J = 6.0 Hz, 2 H), 4.04 (s, 3 H), 4.13 (s, 2 H),4.17 (d, J = 5.7 Hz, 2 H), 7.27 (s, 1 H), 7.39-7.52 (m, 3 H), 7.77 (d, J= 7.5 Hz, 2 H), 7.91 (s, 1 H), 8.67-8.73 (m, 2 H) II-2-279

(DMSO-d6) δ: 1.12 (dd, J = 8.1, 5.1 Hz, 2 H), 1.49 (dd, J = 8.1, 5.5 Hz,2 H), 3.78 (d, J = 5.7 Hz, 2 H), 4.22 (s, 2 H), 7.39-7.44 (m, 1 H),7.48-7.54 (m, 2 H), 7.77- 7.97 (m, 2 H), 7.88 (d, J = 1.8 Hz, 1 H), 8.39(d, J = 1.8 Hz, 1 H), 8.71 (t, J = 5.4 Hz, 1 H), 8.91 (s, 1 H). II-2-280

(DMSO-d6) δ: 1.15 (t, J = 7.3 Hz, 3 H), 3.41 (q, J = 7.3 Hz, 2 H), 3.84(d, J = 5.9 Hz, 2 H), 4.15-4.21 (m, 4 H), 7.79 (t, J = 7.7 Hz, 1 H),7.86-7.93 (m, 2 H), 8.07 (d, J = 8.4 Hz, 1 H), 8.15 (m, 1 H), 8.21 (m, 1H), 8.54 (d, J = 1.7 Hz, 1 H), 8.65-8.79 (m, 2 H).

TABLE 106 reten- tion No. Structure NMR( δ) time Mass method II-2-281

(DMSO-d6) δ: 1.12 (dd, J = 8.1, 5.1 Hz, 2 H), 1.49 (dd, J = 8.1, 5.5 Hz,2 H), 3.76 (d, J = 5.7 Hz, 2 H), 4.07 (s, 2 H), 6.92-7.15 (m, 4 H), 7.30(t, J = 7.6 Hz, 2 H), 7.66 (d, J = 2.4 Hz, 1 H), 7.80 (d, J = 8.9 Hz, 1H), 8.63 (t, J = 5.5 Hz, 1 H), 8.90 (s, 1 H). II-2-282

(DMSO-d6) δ: 2.83 (d, J = 4.5 Hz, 3 H), 3.84 (d, J = 5.9 Hz, 2 H),4.15-4.21 (m, 4 H), 7.58 (t, J = 7.7 Hz, 1 H), 7.81-7.94 (m, 3 H), 8.05(d, J = 8.6 Hz, 1 H), 8.21 (brs, 1 H), 8.46 (d, J = 1.8 Hz, 1 H), 8.58(q, J = 4.7 Hz, 1 H), 8.67-8.77 (m, 2 H). II-2-283

(DMSO-d6) δ: 1.15 (t, J = 7.3 Hz, 3 H), 3.41 (q, J = 7.3 Hz, 2 H), 3.86(d, J = 5.9 Hz, 2 H), 4.18 (s, 2 H), 7.79 (t, J = 7.6 Hz, 1 H), 7.88-7.91 (m, 2 H), 8.07 (d, J = 8.6 Hz, 1 H), 8.15 (d, J = 7.9 Hz, 1 H),8.21 (s, 1 H), 8.54 (d, J = 1.7 Hz, 1 H), 8.73 (t, J = 5.7 Hz, 1 H).II-2-284

(DMSO-d6) δ: 3.83 (d, J = 6.0 Hz, 2 H), 4.04 (s, 3 H), 4.13 (s, 2 H),4.17 (d, J = 5.7 Hz, 2 H), 7.27 (s, 1 H), 7.39-7.52 (m, 3 H), 7.77 (d, J= 7.5 Hz, 2 H), 7.91 (s, 1 H), 8.67-8.73 (m, 2 H) II-2-285

(DMSO-d₆) δ: 3.85 (d, J = 6.08 Hz, 2 H), 4.17 (s, 2 H), 7.81 (dd, J =8.11, 1.52 Hz, 1 H), 7.93-8.03 (m, 4 H), 8.20 (d, J = 8.11 Hz, 1 H),8.33 (d, J = 1.52 Hz, 1 H), 8.72 (t, J = 5.58 Hz, 1 H).

TABLE 107 reten- tion No. Structure NMR(δ) time Mass method II-2-286

(DMSO-d₆) δ: 3.83 (d, J = 5.58 Hz, 2 H), 4.16-4.19 (m, 4 H), 7.81 (dd, J= 8.11, 1.52 Hz, 1 H), 7.94-8.02 (m, 4 H), 8.20 (d, J = 8.11 Hz, 1 H),8.33 (d, J = 1.52 Hz, 1 H), 8.69 (t, J = 5.32 Hz, 1 H), 8.74 (t, J =5.83 Hz, 1.0 H). II-2-287

(DMSO-d₆) δ: 1.12 (dd, J = 8.11, 5.58 Hz, 2 H), 1.49 (dd, J = 8.11, 5.58Hz, 2 H), 3.78 (d, J = 5.58 Hz, 2 H), 4.18 (s, 2 H), 7.81 (dd, J = 8.11,1.52 Hz, 1 H), 7.94- 8.03 (m, 4 H), 8.20 (d, J = 8.11 Hz, 1 H), 8.33 (d,J = 1.52 Hz, 1 H), 8.69 (t, J = 5.58 Hz, 1 H), 8.91 (s, 1 H). II-2-288

(DMSO-d₆) δ: 1.33 (s, 9 H), 3.85 (d, J = 5.58 Hz, 2 H), 4.15 (s, 2 H),7.51 (d, J = 8.11 Hz, 2 H), 7.67-7.73 (m, 3 H), 8.12 (d, J = 8.11 Hz, 1H), 8.19 (d, J = 1.52 Hz, 1 H), 8.71 (t, J = 5.83 Hz, 1 H). II-2-289

(DMSO-d₆) δ: 3.85 (d, J = 6.08 Hz, 2 H), 4.17 (s, 2 H), 7.48 (d, J =8.62 Hz, 2 H), 7.74 (dd, J = 8.62, 1.52 Hz, 1 H), 7.90 (d, J = 8.62 Hz,2.0 H), 8.17 (d, J = 8.62 Hz, 1 H), 8.25 (d, J= 1.52 Hz, 1 H), 8.72 (t,J = 5.83 Hz, 1 H), 12.64 (brs, 1 H). II-2-290

(DMSO-d₆) δ: 1.12 (dd, J = 8.36, 5.32 Hz, 2 H), 1.33 (s, 9 H), 1.49 (dd,J = 8.36, 5.32 Hz, 2 H), 3.77 (d, J = 6.08 Hz, 2 H), 4.16 (s, 2 H), 7.51(d, J = 8.62 Hz, 2 H), 7.73-7.67 (m, 3 H), 8.12 (d, J = 8.11 Hz, 1 H),8.19 (d, J = 1.52 Hz, 1 H), 8.67 (t, J = 5.58 Hz, 1 H), 8.91 (s, 1 H).

TABLE 108 reten- tion No. Structure NMR(δ) time Mass method II-2-291

(DMSO-d₆) δ: 3.83 (d, J = 5.58 Hz, 2 H), 4.15-4.19 (m, 4 H), 7.49 (d, J= 8.62 Hz, 2 H), 7.75 (dd, J = 8.11, 1.52 Hz, 1 H), 7.90 (d, J = 9.12Hz, 2 H), 8.17 (d, J = 8.11 Hz, 1 H), 8.25 (d, J = 1.52 Hz, 1 H), 8.69(t, J = 5.83 Hz, 1 H), 8.74 (t, J = 5.58 Hz, 1 H). II-2-292

(DMSO-d₆) δ: 1.12 (dd, J = 8.36, 5.32 Hz, 2 H), 1.49 (dd, J = 8.36, 5.32Hz, 2 H), 3.78 (d, J = 6.08 Hz, 2 H), 4.17 (s, 2 H), 7.49 (d, J = 8.62Hz, 2 H), 7.75 (dd, J = 8.11, 1.52 Hz, 1 H), 7.90 (d, J = 8.62 Hz, 2 H),8.17 (d, J = 8.11 Hz, 1 H), 8.25 (d, J = 1.52 Hz, 1 H), 8.68 (t, J =5.83 Hz, 1 H), 8.92 (s, 1 H). II-2-293

(DMSO-d₆) δ: 2.08 (s, 3 H), 3.85 (d, J = 6.08 Hz, 2 H), 4.15 (s, 2 H),7.68-7.74 (m, 5 H), 8.11 (d, J = 8.62 Hz, 1 H), 8.18 (d, J = 1.52 Hz, 1H), 8.71 (t, J = 5.58 Hz, 1 H), 10.05 (s, 1 H). II-2-294

(DMSO-d6) δ: 0.86-1.12 (m, 3 H), 3.82 (dd, J = 5.7, 3.3 Hz, 2 H), 4.22(s, 2 H), 4.56 and 4.81 (m, 1 H), 7.39-7.44 (m, 1 H), 7.48- 7.53 (m, 2H), 7.88 (d, J = 1.8 Hz, 1 H), 8.17 (d, J = 8.9 Hz, 1 H), 8.63 (t, J =1.8 Hz, 1 H), 8.67 (d, J = 1.8 Hz, 1 H). II-2-295

(DMSO-d₆) δ: 2.07 (s, 3 H), 3.83 (d, J = 6.08 Hz, 2 H), 4.14-4.19 (m, 4H), 7.69-7.73 (m, 5 H), 8.11 (d, J = 8.62 Hz, 1 H), 8.18 (d, J = 1.52Hz, 1 H), 8.69 (t, J = 5.58 Hz, 1 H), 8.73 (t, J = 5.58 Hz, 1 H), 10.05(s, 1 H).

TABLE 109 reten- tion No. Structure NMR(δ) time Mass method II-2-296

(DMSO-d₆) δ: 1.12 (dd, J = 8.11, 5.58 Hz, 2 H), 1.49 (dd, J = 8.11, 5.58Hz, 2 H), 2.07 (s, 3 H), 3.77 (d, J = 5.58 Hz, 2 H), 4.15 (s, 2 H),7.67-7.74 (m, 5 H), 8.11 (d, J = 8.62 Hz, 1 H), 8.18 (d, J = 1.01 Hz, 1H), 8.67 (t, J = 5.83 Hz, 1 H), 8.92 (s, 1 H), 10.05 (s, 1 H). II-2-297

(DMSO-d₆) δ: 3.83 (d, J = 5.58 Hz, 2 H), 4.14-4.19 (m, 4 H), 7.29 (m, 1H), 7.38- 7.42 (m, 4 H), 7.64 (d, J = 7.60 Hz, 2 H), 7.73 (dd, J = 8.62,1.15 Hz, 1 H), 8.05 (d, J = 8.62 Hz, 1 H), 8.15 (d, J = 1.15 Hz, 1 H),8.69 (t, J = 5.58 Hz, 1 H), 8.73 (t, J = 5.83 Hz, 1 H). II-2-298

(DMSO-d₆) δ: 3.84 (d, J = 5.58 Hz, 2 H), 4.17 (d, J = 5.58 Hz, 2.0 H),4.20 (s, 2 H), 7.65-7.47 (m, 5 H), 7.83 (d, J = 8.62 Hz, 1 H), 7.98-8.05(m, 3 H), 8.21 (d, J = 8.11 Hz, 1 H), 8.69 (t, J = 5.32 Hz, 1 H), 8.75(t, J = 5.83 Hz, 1 H). II-2-299

(DMSO-d6) δ: 1.13 (dd, J = 8.36, 5.32 Hz, 2 H), 1.49 (dd, J = 8.36, 5.32Hz, 2 H), 3.79 (d, J = 5.58 Hz, 2 H), 4.19 (s, 2 H), 7.47-7.65 (m, 5 H),7.83 (d, J = 8.11 Hz, 1 H), 7.98-8.05 (m, 3 H), 8.21 (d, J = 8.11 Hz, 1H), 8.70 (t, J = 5.83 Hz, 1 H), 8.92 (s, 1 H). II-2-300

3.04 (s, 3 H), 3.83 (d, J = 5.58 Hz, 2.0 H), 4.15-4.19 (m, 4.0 H), 7.33(d, J = 8.62 Hz, 2 H), 7.71 (dd, J = 8.11, 1.52 Hz, 1 H), 7.76 (d, J =8.62 Hz, 2 H), 8.12 (d, J = 8.11 Hz, 1 H), 8.19 (d, J = 1.52 Hz, 1 H),8.68 (t, J = 5.58 Hz, 1 H), 8.73 (t, J = 5.83 Hz, 1 H), 9.87 (s, 1 H).

TABLE 110 reten- tion No. Structure NMR(δ) time Mass method II-2-301

(DMSO-d₆) δ: 1.12 (dd, J = 8.36, 5.32 Hz, 2 H), 1.49 (dd, J = 8.36, 5.32Hz, 2 H), 3.77 (d, J = 5.58 Hz, 2 H), 4.14 (s, 2 H), 7.29 (m, 1 H),7.35-7.45 (m, 4 H), 7.64 (d, J = 7.60 Hz, 2 H), 7.73 (dd, J = 8.62, 1.52Hz, 1 H), 8.05 (d, J = 8.62 Hz, 1 H), 8.14 (d, J = 1.52 Hz, 1 H), 8.67(t, J = 5.58 Hz, 1 H), 8.91 (s, 1 H). II-2-302

(DMSO-d6) δ: 3.82 (d, J = 5.7 Hz, 2 H), 4.13 (s, 2 H), 4.16 (d, J = 5.7Hz, 2 H), 7.05 (d, J = 9.7 Hz, 2 H), 7.13-7.20 (m, 2 H), 7.37- 7.44 (m,2 H), 7.52 (d, J = 2.4 Hz, 1 H), 8.07 (d, J = 8.7 Hz, 1 H), 8.64-8.74(m, 2 H). II-2-303

(DMSO-d6) δ: 3.84 (d, J = 5.6 Hz, 2 H), 4.17 (d, J = 5.6 Hz, 2 H), 4.22(s, 2 H), 6.32 (t, J = 2.0 Hz, 1 H), 7.07- 7.11 (m, 2 H), 7.28-7.31 (m,3 H), 7.55 (d, J = 2.0 Hz, 1 H), 7.60 (d, J = 1.5 Hz, 1 H), 8.05 (s, 1H), 8.24 (s, 1 H), 8.69 (t, J = 5.6 Hz, 1 H), 8.75 (t, J = 5.8 Hz, 1 H).II-2-304

(DMSO-d6) δ: 1.11 (dd, J = 8.2, 5.5 Hz, 2 H), 1.48 (dd, J = 8.2, 5.4 Hz,2 H), 3.76 (d, J = 5.7 Hz, 2 H), 4.13 (s, 2 H), 7.06 (d, J = 5.4 Hz, 2H), 7.13-7.20 (m, 2 H), 7.37-7.45 (m, 2 H), 7.51 (d, J = 2.4 Hz, 1 H),8.08 (d, J = 8.7 Hz, 1 H), 8.66 (t, J = 5.5 Hz, 1 H), 8.90 (s, 1 H).II-2-305

(DMSO-d6) δ: 3.83 (d, J = 5.7 Hz, 2 H), 4.14-4.20 (m, 4 H), 7.50-7.67(m, 2 H), 7.79-7.93 (m, 2 H), 8.02 (d, J = 8.6 Hz, 1 H), 8.43 (d, J =1.7 Hz, 1 H), 8.65-8.77 (m, 2 H).

TABLE 111 retention No. Structure NMR (δ) time Mass method II-2-306

(DMSO-d6) δ: 1.12 (dd, J = 8.4, 5.5 Hz, 2H), 1.50 (dd, J = 8.4, 5.4 Hz,2H), 3.78 (d, J = 5.9 Hz, 2H), 4.17 (s, 2H), 7.26 (tt, J = 9.2, 2.2 Hz,1H), 7.51-7.60 (m, 2H), 7.88 (dd, J = 8.6, 1.8 Hz, 1H), 8.03 (d, J = 8.6Hz, 1H), 8.51 (d, J = 1.8 Hz, 1H), 8.69 (t, J = 5.6 Hz, 1H), 8.92 (s,1H). II-2-307

(DMSO-d₆) δ: 3.84 (d, J = 6.08 Hz, 2H), 3.86 (s, 3H), 4.12 (s, 2H), 7.19(m, 1H), 7.33-7.39 (m, 2H), 7.46 (m, 1H), 7.65 (s, 1H), 8.00 (s, 1H),8.68 (t, J = 5.58 Hz, 1H), 12.63 (s, 1H). II-2-308

(DMSO-d₆) δ: 3.84 (d, J = 5.05 Hz, 2H), 3.87 (s. 3H), 4.14 (s, 2H), 4.18(d, J = 5.56 Hz, 2H), 7.20 (m, 1H), 7.337-.51 (m, 2H), 7.65 (s, (s, 1H),8.66-8.73 (m, 2H). II-2-309

(DMSO-d₆) δ: 3.85 (d, J = 5.88 Hz, 2H), 3.88 (s, 3H), 4.13 (s, 2H),7.19-7.32 (m, 3H), 7.66 (s, 1H), 8.06 (s, 1H), 8.69 (t, J = 5.79 Hz,1H), 12.64 (s, 1H) II-2-310

(DMSO-d₆) δ: 3.82-3.88 (m, 5H), 4.13 (s, 2H), 7.40-7.59 (m, 4H), 7.65(s, 1H), 8.00 (s, 1H), 8.69 (t, J = 5.58 Hz, 1H).

TABLE 112 reten- tion No. Structure NMR(δ) time Mass method II-2-311

(DMSO-d₆) δ: 3.83 (d, J = 5.71 Hz, 2 H), 3.86 (s, 3 H), 4.14 (s, 2 H),4.18 (d, J = 5.54 Hz, 2 H), 7.40-7.52 (m, 3 H), 7.57 (m, 1.0 H), 7.65(s, 1 H), 8.00 (s, 1 H), 8.65-8.75 (m, 2 H). II-2-312

(DMSO-d₆) δ: 3.83 (d, J = 5.37 Hz, 2 H), 3.88 (s, 3 H), 4.15 (s, 2 H),4.17 (d, J = 5.37 Hz, 2 H), 7.19-7.31 (m, 3 H), 7.66 (s, 1 H), 8.06 (s,1 H), 8.64-8.76 (m, 2 H). II-2-313

(DMSO-d6) δ: 3.84 (d, J = 5.7 Hz, 2 H), 4.17 (d, J = 5.7 Hz, 2 H), 4.23(s, 2 H), 8.71-8.61 (m, 3 H), 8.89 (d, J = 2.1 Hz, 1 H). II-2-314

(DMSO-d6) δ: 1.13 (dd, J = 8.7, 5.7 Hz, 2 H), 1.49 (dd, J = 8.7, 5.7 Hz,2 H), 3.77 (d, J = 5.7 Hz, 2 H), 4.22 (s, 2 H), 7.33-7.39 (m, 1 H),7.81-7.92 (m, 2 H), 8.25 (d, J = 8.1 Hz, 1 H), 8.45 (d, J = 8. Hz, 1 H),8.71 (t, J = 5.4 Hz, 1 H), 8.92 (s, 1 H). II-2-315

(DMSO-d6) δ: 3.85 (d, J = 5.7 Hz, 2 H), 4.16 (d, J = 5.7 Hz, 2 H), 4.23(s, 2 H), 7.30-7.36 (m, 2 H), 7.88 (d, J = 1.8 Hz, 1 H), 8.37 (d, J =1.8 Hz, 1 H), 8.68 (t, J = 5.7 Hz, 1 H), 8.76 (t, J = 5.7 Hz, 1 H).

TABLE 113 reten- tion No. Structure NMR(δ) time Mass method II-2-316

(DMSO-d6) δ: 1.13 (dd, J = 8.7, 5.7 Hz, 2 H), 1.50 (dd, J = 8.7, 5.7 Hz,2 H), 3.79 (d, J = 5.7 Hz, 2 H), 4.21 (s, 2 H), 7.30-7.36 (m, 2 H),7.81-7.56 (m, 2 H), 7.88 (d, J = 1.4 Hz, 1 H), 8.37 (d, J = 1.4 Hz, 1H), 8.71 (t, J = 5.7 Hz, 1 H), 8.91 (s, 1 H). II-2-317

(DMSO-d6) δ: 3.86 (d, J = 5.7 Hz, 2 H), 4.20 (s, 2 H), 7.38-7.48 (m, 1H), 7.47- 7.52 (m, 2 H), 7.66 (d, J = 1.8 Hz, 1 H), 7.77-7.79 (m, 2 H),8.26 (d, J = 5.4 Hz, 1 H), 8.74 (t, J = 5.7 Hz, 1 H), 12.66 (brs, 1 H).II-2-318

(DMSO-d6) δ: 3.87 (d, J = 5.7 Hz, 2 H), 4.22 (s, 2 H), 7.39-7.53 (m, 1H), 7.77 (d, J = 5.4 Hz, 2 H), 7.89 (d, J = 1.8 Hz, 1 H), 8.39 (d, J =1.4 Hz, 1 H), 8.75 (t, J = 5.7 Hz, 1 H), 12.66 (brs, 1 H). II-2-319

(DMSO-d6) δ: 3.86 (d, J = 5.7 Hz, 2 H), 4.21 (s, 2 H), 7.30-7.69 (m, 1H), 7.81- 7.83 (m, 2 H), 7.89 (d, J = 1.8 Hz, 1 H), 8.37 (d, J = 1.8 Hz,1 H), 8.75 (t, J = 5.7 Hz, 1 H), 12.63 (brs, 1 H). II-2-320

(DMSO-d6) δ: 3.29 (s, 3 H), 3.81 (d, J = 6.0 Hz, 2 H), 4.06 (s, 2 H),4.16 (d, J = 5.5 Hz, 2 H), 7.00 (dd, J = 8.7, 2.4 Hz, 1 H), 7.07- 7.22(m, 4 H), 7.56 (d, J = 2.4 Hz, 1 H), 7.76 (d, J = 8.9 Hz, 1 H),8.63-8.71 (m, 2 H).

TABLE 114 retention No. Structure NMR(δ) time Mass method II-2-321

(DMSO-d₆) δ: 2.80(t, J = 5.83 Hz, 2H), 3.65(t, J = 5.83 Hz, 2H), 3.78(d,J = 5.58 Hz, 2H), 3.91(s, 2H), 4.15(d, J = 5.58 Hz, 2H), 4.46(s, 2H),6.76(t, J = 7.35 Hz, 1H), 7.02(d, J = 8.11 Hz, 2H), 7.21(dd, J = 8.11,7.35 Hz, 2H), 8.58(t, J = 5.83 Hz, 1H), 8.64(t, J = 5.58 Hz, 1H).II-2-322

(DMSO-d₆) δ: 1.13(dd, J = 8.36, 5.32 Hz, 2H), 1.50 (dd, J = 8.36, 5.32Hz, 2H), 3.77(d, J = 6.08 Hz, 2H), 3.84(s, 3H), 4.12(s, 2H), 7.35(m,1H), 7.40-7.46(m, 2H), 7.52(d, J = 7.10 Hz, 2H), 7.63(s, 1H), 7.94(s,1H), 8.64(t, J = 5.83 Hz, 1H), 8.91(s, 1H). II-2-323

(DMSO-d₆) δ: 3.13(t, J = 2.53 Hz, 1H), 3.78(d, J = 5.58 Hz, 2H), 3.85(s,3H), 3.91(dd, J = 5.58, 2.53 Hz, 2H), 4.12(s, 2H), 7.35(m, 1H),7.40-7.45(m, 2H), 7.48-7.54(m, 2H), 7.63(s, 1H), 7.94(s, 1H), 8.43(t, J= 5.58 Hz, 1H), 8.64(t, J = 5.58 Hz, 1H). II-2-324

(DMSO-d6) δ: 3.86(d, J = 5.7 Hz, 2H), 4.22(s, 2H), 7.22-7.28(m, 1H),7.63- 7.69(m, 2H), 7.95(d, J = 1.4 Hz, 1H), 8.45(d, J = 1.4 Hz, 1H),8.76(t, J = 5.4 Hz, 1H), 12.66(brs, 1H). II-2-325

(DMSO-d6) δ: 3.87(d, J = 5.7 Hz, 2H), 4.23(s, 2H), 7.22-7.32(m, 1H),7.58- 7.26(m, 2H), 8.02(d, J = 1.2 Hz, 1H), 8.50(d, J = 0.9 Hz, 1H),8.76(t, J = 5.4 Hz, 1H), 12.66(brs, 1H).

TABLE 115 retention No. Structure NMR(δ) time Mass method II-2-326

(DMSO-d6) δ: 3.85(d, J = 5.7 Hz, 2H), 4.17(d, J = 5.4 Hz, 2H), 4.24(s,2H), 7.22-7.28(m, 1H), 7.64- 7.69(m, 2H), 7.95(s, 1H), 8.45(s, 1H),8.69(t, J = 5.4 Hz, 1H), 8.78(t, J = 5.4 Hz, 1H). II-2-327

(DMSO-d6) δ: 3.85(d, J = 5.7 Hz, 2H), 4.17(d, J = 5.4 Hz, 2H), 4.24(s,2H), 7.44-7.28(m, 1H), 7.50- 7.58(m, 1H), 7.64-7.69(m, 2H), 7.95(s, 1H),8.45(s, 1H), 8.69(t, J = 5.4 Hz, 1H), 8.78(t, J = 5.4 Hz, 1H). II-2-328

(DMSO-d6) δ: 1.77(s, 3H), 3.78(d, J = 5.2 Hz, 2H), 3.83-3.89(m, 2H),4.16(s, 2H), 7.36-7.43(m, 1H), 7.46-7.53(m, 2H), 7.72-7.82(m, 3H),8.02(d, J = 8.4 Hz, 1H), 8.33-8.40 (m, 2H), 8.62-8.68(m, 1H). II-2-329

(DMSO-d6) δ: 3.65(s, 3H), 3.82(d, J = 5.6 Hz, 2H), 4.12(s, 2H), 7.24(t,J = 7.1 Hz, 1H), 7.31-7.41 (m, 5H), 7.91(d, J = 8.6 Hz, 1H), 8.06(d, J =2.0 Hz, 1H), 8.67(t, J = 5.6 Hz, 1H), 12.63(br s, 1H). II-2-330

(DMSO-d6) δ: 3.65(s, 3H), 3.81(d, J = 5.6 Hz, 2H), 4.13(s, 2H), 4.16(d,J = 5.6 Hz, 2H), 7.24(t, J = 7.1 Hz, 1H), 7.31-7.41(m, 5H), 7.92(d, J =8.6 Hz, 1H), 8.06(d, J = 2.0 Hz, 1H), 8.65-8.71(m, 2H).

TABLE 116 retention No. Structure NMR(δ) time Mass method II-2-331

(DMSO-d6) δ: 1.12(dd, J = 7.8 Hz, 2H), 1.48(dd, J = 7.8 Hz, 2H), 3.78(d,J = 5.4 Hz, 2H), 4.22(s, 2H), 4.24 (s, 2H), 7.22-7.28(m, 1H),7.64-7.69(m, 2H), 7.95(d, J = 1.8 Hz, 1H), 8.45(d, J = 1.8 Hz, 1H),8.71(t, J = 5.4 Hz, 1H), 8.91(s, 1H). II-2-332

(DMSO-d6) δ: 1.12(dd, J = 7.8 Hz, 2H), 1.48(dd, J = 7.8 Hz, 2H), 3.78(d,J = 5.4 Hz, 2H), 4.22(s, 2H), 4.24 (s, 2H), 7.22-7.28(m, 1H),7.64-7.69(m, 2H), 7.95(d, J = 1.8 Hz, 1H), 8.71(t, J = 5.4 Hz, 1H),8.91(s, 1H). II-2-333

(DMSO-d₆) δ: 1.12(dd, J = 8.36, 5.32 Hz, 2H), 1.49 (dd, J = 8.36, 5.32Hz, 2H), 3.77(d, J = 6.08 Hz, 2H), 4.17(s, 2H), 7.42-7.47(m, 3H),7.56-7.63(m, 3H), 8.11-8.15(m, 2H), 8.69(t, J = 5.58 Hz, 1H), 8.91(s,1H). II-2-334

(DMSO-d₆) δ: 3.83(d, J = 5.58 Hz, 2H), 4.15-4.19(m, 4H), 7.42-7.48(m,3H), 7.56-7.63(m, 3H), 8.10- 8.15(m, 2H), 8.68(t, J = 5.32 Hz, 1H),8.74(t, J = 5.83 Hz, 1H). II-2-335

(DMSO-d₆) δ: 3.61(s, 3H), 3.69(d, J = 5.07 Hz, 2H), 3.84(s, 3H), 4.11(s,2H), 7.35(m, 1H), 7.40- 7.46(m, 2H), 7.49-7.53(m, 2H), 7.62(s, 1H),7.94(s, 1H), 8.66(t, J = 5.07 Hz, 1H), 11.26(brs, 1H).

TABLE 117 reten- tion meth- No. Structure NMR(δ) time Mass od II-2-336

(DMSO-d₆) δ: 3.84(s, 3H), 3.98(d, J = 5.58 Hz, 2H), 4.16(s, 2H), 7.05(m,1H), 7.28-7.63(m, 10H), 7.94(s, 1H), 8.71(t, J = 5.58 Hz, 1H), 10.01(s,1H). II-2-337

(DMSO-d₆) δ: 1.30(t, J = 6.84 Hz, 3H), 3.83(s, 3H), 3.92-4.01(m, 4H),4.16(s, 2H), 6.87(d, J = 8.62 Hz, 2H), 7.32-7.53(m, 7H), 7.61(s, 1H),7.94(s, 1H), 8.70(t, J = 5.32 Hz, 1H), 9.86(s, 1H). II-2-338

(DMSO-d6) δ: 1.11(dd, J = 8.4, 5.3 Hz, 2H), 1.48(dd, J = 8.4, 5.3 Hz,2H), 3.65(s, 3H), 3.75(d, J = 5.6 Hz, 2H), 4.12(s, 2H), 7.24(t, J = 7.1Hz, 1H), 7.31-7.41 (m, 5H), 7.91(d, J = 8.6 Hz, 1H), 8.06(d, J = 2.0 Hz,1H), 8.64(t, J = 5.8 Hz, 1H), 8.89(s, 1H). II-2-339

(DMSO-d6) δ: 3.19(s, 3H), 3.82(d, J = 6.1 Hz, 2H), 4.08(s, 2H), 4.16(d,J = 5.6 Hz, 2H), 7.25(dd, J = 8.6, 2.0 Hz, 1H), 7.32(d, J = 7.6 Hz, 1H),7.40(dd, J = 7.9, 1.8 Hz, 1H), 7.48-7.54 (m, 2H), 7.80(d, J = 2.5 Hz,1H), 7.86(d, J = 9.1 Hz, 1H), 8.65-8.70(m, 2H), 8.82(s, 1H). II-2-340

(DMSO-d6) δ: 3.06(s, 3H), 3.80(d, J = 5.9 Hz, 2H), 4.00(s, 2H), 4.16(d,J = 5.7 Hz, 2H), 4.65(s, 2H), 6.96(dd, J = 9.1, 2.4 Hz, 1H),7.17-7.35(m, 6H), 7.69(d, J = 9.1 Hz, 1H), 8.60-8.69(m, 2H).

TABLE 118 retention No. Structure NMR(δ) time Mass method II-2-341

(DMSO-d₆) δ: 3.82-3.86 (m, 5H), 4.12(s, 2H), 7.35 (m, 1H), 7.40-7.53(m,4H), 7.63(s, 1H), 7.94(s, 1H), 8.67(t, J = 5.58 Hz, 1H), 12.62(s, 1H).II-2-342

(DMSO-d₆) δ: 3.06-2.92 (m, 4H), 3.81(d, J = 5.58 Hz, 2H), 4.11(s, 2H),4.16 (d, J = 5.58 Hz, 2H), 7.14- 7.31(m, 6.0H), 7.77(s, 1H), 7.93(d, J =8.11 Hz, 1H), 8.64-8.72(m, 2H). II-2-343

(DMSO-d₆) δ: 1.12(dd, J = 8.11, 5.58 Hz, 2H), 1.49 (dd, J = 8.11, 5.58Hz, 2H), 2.92-3.07(m, 4H), 3.76(d, J = 5.58 Hz, 2H), 4.10(s, 2H),7.14-7.31(m, 6H), 7.77(s, 1H), 7.93(d, J = 8.11 Hz, 1H), 8.64(t, J =5.58 Hz, 1H), 8.90(s, 1H). II-2-344

(DMSO-d6) δ: 3.87(d, J = 5.7 Hz, 2H), 4.16(d, J = 5.4 Hz, 2H), 4.31(s,2H), 7.54-7.62(m, 3H), 8.22(d, J = 8.1 Hz, 1H), 8.73(t, J = 5.7 Hz, 1H),8.83(t, J = 5.7 Hz, 1H), 9.366(s, 1H). II-2-345

(DMSO-d6) δ: 1.20-1.55 (m, 5H), 1.66-1.91(m, 5H), 2.64(m, 1H), 3.83(d, J= 5.9 Hz, 2H), 4.09(s, 2H), 7.36(dd, J = 8.4, 1.7 Hz, 1H), 7.84(d, J =8.4 Hz, 1H), 7.89(d, J = 1.7 Hz, 1H), 8.66(t, J = 5.8 Hz, 1H).

TABLE 119 retention No. Structure NMR(δ) time Mass method II-2-346

(DMSO-d6) δ: 1.22-1.56 (m, 5H), 1.66-1.91(m, 5H), 2.64(m, 1H), 3.81(d, J= 5.9 Hz, 2H), 4.10(s, 2H), 4.16(d, J = 5.5 Hz, 2H), 7.36(dd, J = 8.6,1.7 Hz, 1H), 7.84(d, J = 8.6 Hz, 1H), 7.89(d, J = 1.5 Hz, 1H),8.62-8.72(m, 2H). II-2-347

(DMSO-d6) δ: 3.86(d, J = 6.1 Hz, 2H), 3.89-3.98(m, 2H), 4.18(s, 2H),7.57(dd, J = 8.1, 5.1 Hz, 1H), 7.87 (dd, J = 8.6, 2.0 Hz, 1H), 8.06(d, J= 8.6 Hz, 1H), 8.23(dt, J = 8.1, 2.0 Hz, 1H), 8.49(d, J = 1.5 Hz, 1H),8.61-8.65(m, 2H), 8.71(t, J = 5.8 Hz, 1H), 9.01(d, J = 2.0 Hz, 1H).II-2-348

(DMSO-d6) δ: 3.83(d, J = 5.6 Hz, 2H), 4.16-4.18(m, 4H), 7.52(dd, J =8.1, 4.6 Hz, 1H), 7.86(dd, J = 8.4, 1.8 Hz, 1H), 8.06(d, J = 8.6 Hz,1H), 8.17(dt, J = 7.9, 1.9 Hz, 1H), 8.48(d,J = 2.0 Hz, 1H), 8.60(dd, J =4.6, 1.5 Hz, 1H), 8.68(t, J = 5.6 Hz, 1H), 8.73(t, J = 5.8 Hz, 1H),8.98(d, J = 2.0 Hz, 1H). II-2-349

(DMSO-d6) δ: 1.12(dd, J = 8.1, 5.6 Hz, 2H), 1.49(dd, J = 8.1, 5.6 Hz,2H), 3.27 (s, 3H), 3.78(d, J = 6.1 Hz, 2H), 4.18(s, 2H), 7.88(dd, J =8.4, 1.8 Hz, 1H), 8.03- 8.07(m, 5H), 8.52(d, J = 2.0 Hz, 1H), 8.69(t, J= 5.8 Hz, 1H), 8.91(s, 1H). II-2-350

(DMSO-d6) δ: 3.81(s, 3H), 3.98(d, J = 5.4 Hz, 2H), 4.20(s, 2H), 6.81(d,J = 9.0 Hz, 1H), 7.39(t, J = 6.9 Hz, 1H), 7.50(t, J = 7.2 Hz, 2H),7.74-7.90(m, 5H), 8.01(d, J = 8.4 Hz, 1H), 8.34-8.39(2H, m), 8.76(1H,m), 10.07(s, 1H)

TABLE 120 retention No. Structure NMR(δ) time Mass method II-2-351

(DMSO-d6) δ: 3.82(d, J = 6.0 Hz, 2H), 4.08(s, 2H), 5.20(s, 2H), 7.13(d,J = 9.0 Hz, 1H), 7.32-7.50(m, 5H), 7.56(s, 1H), 7.92(d, J = 9.0 Hz, 1H),8.66(m, 1H) II-2-352

(DMSO-d6) δ: 3.81(d, J = 5.7 Hz, 2H), 4.09(s, 2H), 4.16(d, J = 5.4 Hz,2H), 5.20(s, 2H), 7.13(d, J = 9.0 Hz, 1H), 7.33-7.50(m, 5H), 7.56(s,1H), 7.92(d, J = 9.0 Hz, 1H), 8.67-8.69(m, 2H) II-2-353

(DMSO-d6) δ: 1.09-1.14 (m, 2H), 1.46-1.51(m, 2H), 3.75(d, J = 6.3 Hz,2H), 4.09(s, 2H), 5.20(s, 2H), 7.13(d, J = 9.0 Hz, 1H), 7.33-7.57(m,6H), 7.93(d, J = 9.0 Hz, 1H), 8.62(m, 1H), 8.67-8.69(m, 2H) II-2-354

(DMSO-d6) δ: 1.97-2.03 (m, 2H), 2.25-2.32(m, 2H), 2.55-2.59(m, 2H),3.81(d, J = 5.7 Hz, 2H), 4.09(s, 2H), 5.20(s, 2H), 7.12(d, J = 9.0 Hz,1H), 7.33-7.56(m, 6H), 7.92(d, J = 9.0 Hz, 1H), 8.62(m, 1H), 8.92(s, 1H)II-2-355

(DMSO-d6) δ: 1.62(m, 2H), 1.75(m, 2H), 2.22(m, 2H), 2.43(m, 2H), 3.82(d,J = 5.9 Hz, 2H), 4.11(s, 2H), 4.16(d, J = 5.4 Hz, 2H), 6.26(m, 1H),7.56(dd, J = 8.6, 1.8 Hz, 1H), 7.86 (d, J = 8.6 Hz, 1H), 8.06(d, J = 1.5Hz, 1H), 8.64-8.73 (m, 2H).

TABLE 121 retention No. Structure NMR(δ) time Mass method II-2-356

(DMSO-d6) δ: 1.12(dd, J = 8.2, 5.5 Hz, 2H), 1.49(dd, J = 8.1, 5.4 Hz,2H), 1.62 (m, 2H), 1.76(m, 2H), 2.21 (m, 2H), 2.44(m, 2H), 3.76 (d, J =5.7 Hz, 2H), 4.11(s, 2H), 6.26(s, 1H), 7.56(dd, J = 8.6, 1.8 Hz, 1H),7.86 (d, J = 8.6 Hz, 1H), 8.06(d, J = 1.5 Hz, 1H), 8.65(t, J = 5.5 Hz,1H), 8.90(s, 1H). II-2-357

(DMSO-d6) δ: 3.83(d, J = 5.7 Hz, 2H), 4.14(s, 2H), 7.26-7.40(m, 5H),7.45(dd, J = 8.5, 1.9 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 8.15(d, J = 1.8Hz, 1H), 8.70(t, J = 5.7 Hz, 1H). II-2-358

(DMSO-d6) δ: 3.82(d, J = 5.9 Hz, 2H), 4.13-4.19(m, 4H), 4.26-7.40(m,5H), 7.45(dd, J = 8.5, 1.9 Hz, 1H), 7.95(d, J = 8.6 Hz, 1H), 8.15(d, J =1.5 Hz, 1H), 8.64-8.76(m, 2H). II-2-359

(DMSO-d6) δ: 1.12(dd, J = 8.2, 5.5 Hz, 2H), 1.49(dd, J = 8.1, 5.5 Hz,2H), 3.76 (d, J = 5.7 Hz, 2H), 4.14(s, 2H), 7.26-7.41(m, 5H), 7.45(dd, J= 8.5, 1.9 Hz, 1H), 7.95(d, J = 8.6 Hz, 1H), 8.15(d, J = 1.8 Hz, 1H),8.67(t, J = 5.4 Hz, 1H), 8.90(s, 1H). II-2-360

(DMSO-d₆) δ: 3.85(d, J = 5.58 Hz, 2H), 4.19(s, 2H), 7.38-7.22(m, 3H),8.19(s, 1H), 8.22(s, 1H), 8.73(t, J = 5.58 Hz, 1H), 12.64(brs, 1H).

TABLE 122 retention No. Structure NMR(δ) time Mass method II-2-361

(DMSO-d₆) δ: 3.85(d, J = 6.08 Hz, 2H), 4.18(s, 2H), 7.26-7.37(m, 3.0H),7.54 (m, 1H), 8.17(s, 1H), 8.19 (s, 1H), 8.73(t, J = 5.58 Hz, 1H),12.65(brs, 1H). II-2-362

(DMSO-d₆) δ: 3.83(d, J = 6.08 Hz, 2H) 4.16(d, J = 5.58 Hz, 2H), 4.20(s,2H), 7.23-7.38(m, 3H), 8.19(s, 1H), 8.22(s, 1H), 8.68(t, J = 5.32 Hz,1H), 8.75(t, J = 5.83 Hz, 1H). II-2-363

(DMSO-d₆) δ: 1.12(dd, J = 8.36, 5.32 Hz, 2H), 1.49 (dd, J = 8.36, 5.32Hz, 2H), 3.78(d, J = 5.58 Hz, 2H), 4.20(s, 2H), 7.23-7.38(m, 3H),8.19(s, 1H), 8.22(s, 1H), 8.70(t, J = 5.58 Hz, 1H), 8.91(s, 1H).II-2-364

(DMSO-d₆) δ: 3.83(d, J = 6.08 Hz, 2H), 4.16(d, J = 5.58 Hz, 2H), 4.19(s,2H), 7.25-7.37(m, 3H), 7.54(m, 1H), 8.17(s, 1H), 8.19(s, 1H), 8.68(t, J= 5.58 Hz, 1H), 8.74(t, J = 5.58 Hz, 1H). II-2-365

(DMSO-d₆) δ: 1.12(dd, J = 8.36, 5.32 Hz, 2H), 1.49 (dd, J = 8.36, 5.32Hz, 2H), 3.77(d, J = 5.58 Hz, 2H), 4.19(s, 2H), 7.25-7.37(m, 3H),7.53(m, 1H), 8.17(s, 1H), 8.19(s, 1H), 8.69(t, J = 5.58 Hz, 1H), 8.91(s,1H).

TABLE 123 retention meth- No. Structure NMR(δ) time Mass od II-2-366

(DMSO-d6) δ: 3.84(d, J = 5.7 Hz, 2H), 4.21(s, 2H), 7.59-7.73(m, 3H),7.95- 8.03(m, 3H), 8.12(d, J = 8.7 Hz, 1H), 8.72(t, J = 5.6 Hz, 1H),8.86(d, J = 1.8 Hz, 1H), 12.65(br s, 1H). II-2-367

1.9 403 C II-2-368

(DMSO-d6) δ: 1.30(t, J = 6.9 Hz, 3H), 3.94-3.98(m, 4H), 4.23(s, 2H),6.87(d, J = 9.0 Hz, 2H), 7.46-7.54(m, 5H), 8.15(t, J = 8.7 Hz, 3H),8.40(t, J = 8.4 Hz, 1H), 8.76 (1H, m), 9.88(s, 1H) II-2-369

(DMSO-d6) δ: 3.85(d, J = 6.1 Hz, 2H), 4.17(d, J = 5.6 Hz, 2H), 4.22(s,2H), 7.44- 7.56(m, 6H), 8.01(d, J = 8.6 Hz, 1H), 8.69(t, J = 5.3 Hz,1H), 8.77(t, J = 5.6 Hz, 1H) II-2-370

(DMSO-d6) δ: 3.82(d, J = 5.7 Hz, 2H), 4.15(d, J = 5.5 Hz, 2H), 4.22(s,2H), 7.57- 7.73(m, 3H), 7.95-8.03(m, 3H), 8.13(d, J = 8.4 Hz, 1h),8.62-8.78(m, 2H), 8.86(m, 1H).

TABLE 124 retention No. Structure NMR(δ) time Mass method II-2-371

(DMSO-d6) δ: 1.13(dd, J = 8.4, 5.3 Hz, 2H), 1.49(dd, J = 8.4, 5.3 Hz,2H), 3.79 (d, J = 5.6 Hz, 2H), 4.21(s, 2H), 7.44-7.56(m, 6H), 8.00(d, J= 8.1 Hz, 1H), 8.71(t, J = 5.8 Hz, 1H), 8.92(s, 1H). II-2-372

(DMSO-d6) δ: 1.12(dd, J = 8.4, 5.3 Hz, 2H), 1.49(dd, J = 8.4, 5.3 Hz,2H), 3.76 (d, J = 5.6 Hz, 2H), 4.12(s, 2H), 5.33(d, J = 10.6 Hz, 1H),5.93(d, J = 17.7 Hz, 1H), 6.85(dd, J = 17.5, 10.9 Hz, 1H), 7.63(dd, J =8.6, 1.5 Hz, 1H), 7.90(d, J = 8.6 Hz, 1H), 8.15(s, 1H), 8.66(t, J = 5.8Hz, 1H), 8.90(s, 1H). II-2-373

(DMSO-d6) δ: 4.21(s, 2H), 4.57(d, J = 5.6 Hz, 2H), 7.12-7.18(m, 2H),7.37-7.57(m, 5H), 7.74- 7.80(m, 3H), 8.02(d, J = 8.6 Hz, 1H), 8.38(d, J= 1.5 Hz, 1H), 9.05(t, J = 5.6 Hz, 1H), 12.30(s, 1H). II-2-374

(DMSO-d6) δ: 4.21(s, 2H), 4.53(d, J = 9.0 Hz, 2H), 5.72(s, 2H), 5.96(d,J = 9.0 Hz, 1H), 7.39(m, 1H), 7.50(t, J = 7.5 Hz, 2H), 7.74-7.81(m, 3H),8.0-8.04 (2H, m), 8.38(s, 1H), 8.80 (m, 1H) II-2-375

1.95 406 C

TABLE 125 reten- tion meth- No. Structure NMR(δ) time Mass od II-2-376

(DMSO-d₆) δ: 1.12(dd, J = 8.11, 5.58 Hz, 2H), 1.49 (dd, J = 8.11, 5.58Hz, 2H), 3.77(d, J = 5.58 Hz, 2H), 4.18(s, 2H), 7.40- 7.52(m, 5H),8.146(s, 1H), 8.154(s, 1H), 8.69(t, J = 5.58 Hz, 1H), 8.91(s, 1H).II-2-377

(DMSO-d₆) δ: 1.30(t, J = 6.84 Hz, 3H), 3.93-4.01(m, 4H), 4.22 (s, 2H),6.84-6.89(m, 2H), 7.42-7.52(m, 7H), 8.15(s, 2H), 8.74(t, J = 5.58 Hz,1H), 9.87(s, 1H). II-2-378

(DMSO-d₆) δ: 1.12(dd, J = 8.11, 5.58 Hz, 2H), 1.49(dd, J = 8.11, 5.58Hz, 2H), 3.83(s, 3H), 4.09(s, 2H), 7.23-7.29(m, 2H), 7.53- 7.59(m, 2H),7.79(s, 1H), 7.80(s, 1H), 8.64(t, J = 5.58 Hz, 1H), 8.90(s, 1H).II-2-379

(DMSO-d6) δ: 1.12(dd, J = 8.1, 5.6 Hz, 2H), 1.49(dd, J = 8.4, 5.3 Hz,2H), 3.77(d, J = 5.6 Hz, 2H), 4.17(s, 2H), 7.30-7.34(m, 2H),7.51-7.56(m, 2H), 7.93 (s, 1H), 8.36(s, 1H), 8.68(t, J = 5.8 Hz, 1H),8.91(s, 1H). II-2-380

(DMSO-d6) δ: 3.83(d, J = 6.1 Hz, 2H), 4.15-4.18(m, 4H), 7.32(t, J = 8.9Hz, 2H), 7.52-7.55(m, 2H), 7.94(s, 1H), 8.36(s, 1H), 8.68(t, J = 5.3 Hz,1H), 8.74(t, J = 5.8 Hz, 1H).

TABLE 126 reten- tion meth- No. Structure NMR(δ) time Mass od II-2-381

(DMSO-d6) δ: 3.84(d, J = 5.9 Hz, 2H), 4.16(d, J = 5.7 Hz, 2H), 4.23(s,2H), 7.34 (m, 2H), 7.45(d, J = 8.2 Hz, 1H), 7.51-7.57(m, 2H), 8.11(d, J= 8.2 Hz, 1H), 8.68(t, J = 5.8 Hz, 1H), 8.77(t, J = 5.7 Hz, 1H).II-2-382

(DMSO-d6) δ: 1.12(dd, J = 8.2, 5.5 Hz, 2H), 1.49(dd, J = 8.2, 5.4 Hz,2H), 3.78 (d, J = 5.7 Hz, 2H), 4.22(s, 2H), 7.34(t, J = 9.0 Hz, 2H),7.44(d, J = 8.2 Hz, 1H), 7.51-7.59(m, 2H), 8.11(d, J = 8.2 Hz, 1H),8.72(t, J = 5.5 Hz, 1H), 8.91(s, 1H). II-2-383

(DMSO-d6) δ: 3.82(d, J = 5.7 Hz, 2H), 4.07(s, 2H), 4.17(d, J = 5.7 Hz,2H), 6.61(td, J = 8.7, 2.4 Hz, 1H), 6.81-6.94(m, 2H), 7.18-7.30(m, 2H),7.77(d, J = 2.2 Hz, 1H), 7.83(d, J = 8.7 Hz, 1H), 8.60(s, 1H),8.63-8.72(m, 2H). II-2-384

2.07 447.3 C II-2-385

(DMSO-d6) δ: 1.52-1.58 (m, 2H), 1.92-1.99(m, 2H), 3.46(t, J = 10.8 Hz,2H), 3.80-3.86(m, 2H), 3.96(d, J = 5.4 Hz, 2H), 4.23(s, 2H), 4.48(m,1H), 6.93(d, J = 9.3 Hz, 2H), 7.46-7.56 (m, 5H), 8.15(t, J = 7.2 Hz,3H), 8.39(d, J = 8.4 Hz, 1H), 8.74(m, 1H), 9.88(s, 1H).

TABLE 127 retention No. Structure NMR(δ) time Mass method II-2-386

(DMSO-d₆) δ: 4.15(d, J = 5.58 Hz, 2H), 4.22(s, 2H), 7.40-7.52(m, 5H),8.15(s, 1H), 8.18(s, 1H), 8.87(t, J = 5.58 Hz, 1H), 9.18(s, 1H),12.68(s, 1H). II-2-387

(DMSO-d6) δ: 3.81(d, J = 6.1 Hz, 2H), 4.04(s, 2H), 4.16(d, J = 6.1 Hz,2H), 6.96(dd, J = 12.9, 6.3 Hz, 1H), 7.11(t, J = 8.1 Hz, 1H), 7.16(dd, J= 8.6, 2.5 Hz, 1H), 7.23(dd, J = 11.7, 8.1 Hz, 1H), 7.33(t, J = 8.1 Hz,1H), 7.53(d, J = 2.0 Hz, 1H), 7.78(d, J = 8.6 Hz, 1H), 8.14(s, 1H),8.62- 8.69(m, 2H). II-2-388

(DMSO-d6) δ: 1.12(dd, J = 8.4, 5.3 Hz, 2H), 1.49(dd, J = 8.4, 5.3 Hz,2H), 1.88 (d, J = 6.1 Hz, 3H), 3.76(d, J = 5.6 Hz, 2H), 4.10(s, 2H),6.35-6.43(m, 1H), 6.53(d, J = 16.7 Hz, 1H), 7.53(dd, J = 8.6, 1.5 Hz,1H), 7.85(d, J = 8.6 Hz, 1H), 8.02(s, 1H), 8.64(t, J = 5.6 Hz, 1H),8.89(s, 1H). II-2-389

(DMSO-d6) δ: 4.00(d, J = 5.7 Hz, 2H), 4.20(s, 2H), 7.39-7.52(m, 3H),7.74- 7.81(m, 3H), 8.03(d, J = 8.4 Hz, 1H), 8.37-8.42(m, 3H), 8.78(br-s,1H), 9.31 (s, 1H), 10.88(s, 1H) II-2-390

(DMSO-d6) δ: 2.34(s, 3H), 4.07(d, J = 5.7 Hz, 2H), 4.19(s, 2H), 7.15(s,1H), 7.38-7.52(m, 3H), 7.74- 7.81(m, 3H), 8.04(d, J = 8.7 Hz, 1H),8.38(s, 1H), 8.79(m, 1H), 12.00(s, 1H)

TABLE 128 retention No. Structure NMR(δ) time Mass method II-2-391

(DMSO-d6) δ: 1.11(dd, J = 8.4, 5.3 Hz, 2H), 1.48(dd, J = 8.4, 5.3 Hz,2H), 3.76 (d, J = 5.6 Hz, 2H), 4.21(s, 2H), 7.59-7.72(m, 3H),7.96-8.01(m, 3H), 8.12(d, J = 8.6 Hz, 1H), 8.68(t, J = 5.6 Hz, 1H),8.86(d, J = 1.5 Hz, 1H), 8.89(s, 1H). II-2-392

(DMSO-d6) δ: 3.11(s, 3H), 3.82(d, J = 5.6 Hz, 2H), 4.09(s, 2H), 4.16(d,J = 5.6 Hz, 2H), 7.18(d, J = 9.1 Hz, 2H), 7.29(dd, J = 8.9, 2.3 Hz, 1H),7.71(d, J = 9.1 Hz, 2H), 7.87-7.92 (m, 2H), 8.69(q, J = 6.1 Hz, 2H),9.05(s, 1H). II-2-393

(DMSO-d6) δ: 3.81(d, J = 6.1 Hz, 2H), 4.06(s, 2H), 4.16(d, J = 5.6 Hz,2H), 7.20(dd, J = 8.9, 2.3 Hz, 1H), 7.26(dd, J = 8.1, 4.6 Hz, 1H),7.52-7.54(m, 1H), 7.74(d, J = 2.5 Hz, 1H), 7.82(d, J = 8.6 Hz, 1H),8.06(d, J = 4.6 Hz, 1H), 8.39(d, J = 3.0 Hz, 1H), 8.56(s, 1H), 8.67(t, J= 4.6 Hz, 2H). II-2-394

1H-NMR (DMSO-d6) δ: 1.12(dd, J = 8.36, 5.32 Hz, 2H), 1.49(dd, J = 8.36,5.32 Hz, 2H), 3.78(d, J = 5.58 Hz, 2H), 4.23(s, 2H), 7.35-7.39(m, 2H),7.45- 7.48(m, 3H), 8.16(s, 1H), 8.36(s, 1H), 8.71(t, J = 5.58 Hz, 1H),8.92(s, 1H). II-2-395

1H-NMR (DMSO-d6) δ: 3.84(d, J = 6.08 Hz, 2H), 4.16(d, J = 5.58 Hz, 2H),4.24(s, 2H), 7.37-7.38(m, 2H), 7.43-7.50(m, 3H), 8.16(s, 1H), 8.36(s,1H), 8.69(t, J = 5.58 Hz, 1H), 8.77(t, J = 5.83 Hz, 1H).

Test Example 1 Evaluation Method of Human Endothelial Lipase (EL)Inhibitory Activity Using Human High-Density Lipoprotein (HDL)

After the present compound dissolved in DMSO was added to become 0.5%DMSO to the reaction buffer consisting of 20 mM tris hydrochloric acid(pH7.4), bovine serum albumin (0.5%), calcium chloride (4 mM), sodiumchloride (150 mM) and human HDL (2 mg/ml), the EL enzyme was added(total volume was 20 μl).

After 4-hour reaction at 37° C., non-esterified fatty acid (NEFA)generated from HDL by EL was measured with a commercially availableassay kit and the amount of NEFA was used as an index of enzymeactivity. Considering the enzyme activity without the inhibitor as acontrol value, the inhibition rate of each concentration of the presentcompound was calculated, and 50% inhibitory concentration (IC50 value)was calculated from an inhibition curve.

The result of Test Example 1 is shown below.

Compound (II-1-1): IC50=0.23 μM Compound (II-1-11): IC50=0.56 μMCompound (II-1-17): IC50=1.3 μM Compound (II-1-190): IC50=2.1 μMCompound (II-1-202): IC50=0.29 μM Compound (II-1-246): IC50=0.28 μMCompound (II-2-1): IC50=0.11 μM Compound (II-2-291): IC50=0.056 μMCompound (II-2-211): IC50=0.032 μM Compound (II-2-67): IC50=0.029 μMCompound (II-2-131): IC50=0.092 μM Compound (II-2-144): IC50=0.029 μM

The present compound selectively inhibits endothelial lipase as shown inTest Example 1, and has high selectivity for hepatic lipase (HL) andlipoprotein lipase (LPL). Selectivity was analyzed by the followingtests.

Test Example 2 Evaluation Method of Human Hepatic Lipase (HL) InhibitoryActivity Using Human Very Low-Density Lipoprotein (VLDL)

After an inhibitor dissolved in DMSO was added to become 0.5% DMSO tothe reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4),bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride(150 mM) and human VLDL (0.5 mg/ml), the HL enzyme was added (totalvolume was 20 μl).

After 4-hour reaction at 37° C., non-esterified fatty acid (NEFA)generated from VLDL by HL was measured with a commercially availableassay kit and the amount of NEFA was used as an index of enzymeactivity. Considering the enzyme activity without the inhibitor as acontrol value, the inhibition rate of each concentration of an inhibitorwas calculated, and 50% inhibitory concentration (IC50 value) wascalculated from an inhibition curve.

Test Example 3 Evaluation Method of Human Lipoprotein Lipase (LPL)Inhibitory Activity Using Human Very Low-Density Lipoprotein (VLDL)

After an inhibitor dissolved in DMSO was added to become 0.5% DMSO tothe reaction buffer consisting of 20 mM tris hydrochloric acid (pH7.4),bovine serum albumin (0.5%), calcium chloride (4 mM), sodium chloride(150 mM) and human VLDL (0.5 mg/ml), the LPL enzyme was added (totalvolume was 20 μl).

After 4-hour reaction at 37° C., non-esterified fatty acid (NEFA)generated from HDL by LPL was measured with a commercially availableassay kit and the amount of NEFA was used as an index of enzymeactivity. Considering the enzyme activity without the inhibitor as acontrol value, the inhibition rate of each concentration of an inhibitorwas calculated, and 50% inhibitory concentration (IC50 value) wascalculated from an inhibition curve.

The results of Test Example 2 and 3 indicated that the present compoundinhibited the endothelial lipase selectively and had high selectivityfor hepatic Lipase (HL) and lipoprotein lipase (LPL).

Serum HDL cholesterol elevating effect can be examined as follows.

Pharmacological Test on HDL Elevating Effect

The C57BL/6J mice at 8-25-weeks old were divided into 5-9 animals pergroup and administered test compound (20-200 mg/kg/day) orally. To thecontrol group, 0.5% methyl cellulose solution (10 mL/kg) of the vehiclewas administered orally. The blood was collected from tail vein beforeand 24-hour after the administration of compound, and serum HDLcholesterol concentration was measured with [koresutesuto] N HDL (Daiitichemical Ltd.). The animals were separated into groups so that the meanvalue of weight and serum HDL cholesterol level become almost equalbetween each examination groups. The efficacy of the test compound wasshown as the rate of changes compared to the values beforeadministration (the HDL cholesterol elevating rate; % Initial), andsignificant differences against the values of control groups wereevaluated.

Usefulness for medicaments can be analyzed by the following examinationsetc.

CYP3A4 Fluorescent MBI Test

The CYP3A4 fluorescent MBI test is a test of investigating enhancementof CYP3A4 inhibition of a compound by a metabolism reaction, and thetest was performed using, as CYP3A4 enzyme expressed in Escherichia coliand employing, as an index, a reaction in which7-benzyloxytrifluoromethylchmarin (7-BFC) is debenzylated by the CYP3A4enzyme to produce a metabolite, 7-hydroxytrifluoromethylchmarin (HFC)emitting fluorescent light.

The reaction conditions were as follows: substrate, 5.6 μmol/L 7-BFC;pre-reaction time, 0 or 30 minutes; reaction time, 15 minutes; reactiontemperature, 25° C. (room temperature); CYP3A4 content (enzyme expressedin Escherichia coli), at pre-reaction 62.5 μmol/mL, at reaction 6.25μmol/mL (at 10-fold dilution); test drug concentration, 0.625, 1.25,2.5, 5, 10, 20 μmol/L (six points).

An enzyme in a K-Pi buffer (pH 7.4) and a test drug solution as apre-reaction solution were added to a 96-well plate at the compositionof the pre-reaction, a part of it was transferred to another 96-wellplate so that it was 1/10 diluted with a substrate and a K-Pi buffer,NADPH as a co-factor was added to initiate a reaction as an index(without preincubation) and, after a predetermined time of a reaction,acetonitrile/0.5 mol/L Tris (trishydroxyaminomethane)=4/1 was added tostop the reaction. In addition, NADPH was added to a remainingpreincubation solution to initiate a preincubation (with preincubation)and, after a predetermined time of a preincubation, a part wastransferred to another plate so that it was 1/10 diluted with asubstrate and a K-Pi buffer to initiate a reaction as an index. After apredetermined time of a reaction, acetonitrile/0.5 mol/L Tris(trishydroxyaminomethane)=4/1 was added to stop the reaction. For theplate on which each index reaction had been performed, a fluorescentvalue of 7-HFC which is a metabolite was measured with a fluorescentplate reader. (Ex=420 nm, Em=535 nm).

Addition of only DMSO which is a solvent dissolving a drug to a reactionsystem was adopted as a control (100%), remaining activity (%) wascalculated at each concentration of a test drug added as the solution,and IC₅₀ was calculated by reverse-presumption by a logistic model usinga concentration and an inhibition rate. When a difference between IC₅₀values is 5 μM or more, this was defined as (+) and, when the differenceis 3 μM or less, this was defined as (−).

CYP Inhibition Test

Using commercially available pooled human hepatic microsome, andemploying, as markers, 7-ethoxyresorufin O-deethylation (CYP1A2),tolbutamide methyl-hydroxylation (CYP2C9), mephenyloin 4′-hydroxylation(CYP2C19), dextromethorphan O-demethylation (CYP2D6), and terfenedinehydroxylation (CYP3A4) as typical substrate metabolism reactions ofhuman main five CYP enzyme forms (CYP1A2, 2C9, 2C19, 2D6, 3A4), aninhibitory degree of each metabolite production amount by a testcompound was assessed.

The reaction conditions were as follows: substrate, 0.5 μmol/Lethoxyresorufin (CYP1A2), 100 μmol/L tolbutamide (CYP2C9), 50 μmol/LS-mephenitoin (CYP2C19), 5 μmol/L dextromethorphan (CYP2D6), 1 μmol/Lterfenedine (CYP3A4); reaction time, 15 minutes; reaction temperature,37° C.; enzyme, pooled human hepatic microsome 0.2 mg protein/mL; testdrug concentration, 1, 5, 10, 20 μmol/L (four points).

Each five kinds of substrates, human hepatic microsome, or a test drugin 50 mM Hepes buffer as a reaction solution was added to a 96-wellplate at the composition as described above, NADPH, as a cofactor wasadded to initiate metabolism reactions as markers and, after theincubation at 37° C. for 15 minutes, a methanol/acetonitrile=1/1 (v/v)solution was added to stop the reaction. After the centrifugation at3000 rpm for 15 minutes, resorufin (CYP1A2 metabolite) in thesupernatant was quantified by a fluorescent multilabel counter andtributamide hydroxide (CYP2C9 metabolite), mephenyloin 4′ hydroxide(CYP2C19 metabolite), dextromethorphan (CYP2D6 metabolite), andterfenadine alcohol (CYP3A4 metabolite) were quantified by LC/MS/MS.

Addition of only DMSO being a solvent dissolving a drug to a reactionsystem was adopted as a control (100%), remaining activity (%) wascalculated at each concentration of a test drug added as the solutionand IC₅₀ was calculated by reverse presumption by a logistic model usinga concentration and an inhibition rate.

Solubility Test

The solubility of a compound was determined under a condition in which1% DMSO was added. 10 mM compound solution was prepared using DMSO, andthen 6 μL of the compound solution was added to 594 μL of artificialintestinal juice in pH 6.8 (to 250 mL of 0.2 mol/L potassium dihydrogenphosphate reagent solution was added 118 mL of 0.2 mol/L NaOH reagentsolution and water to provide a final volume of 1000 mL). After standingat 25 degrees Celsius for 16 hours, the mixed solution was filtratedwith suction. The filtrate was diluted twice with methanol/water (1/1),and then a concentration in the filtration was measured with HPLC orLC/MS/MS by the absolute calibration method.

Metabolism Stability Test

Using commercially available pooled human hepatic microsomes, a testcompound was reacted for a constant time, a remaining rate wascalculated by comparing a reacted sample and an unreacted sample,thereby, a degree of metabolism in liver was assessed.

A reaction was performed (oxidative reaction) at 37° C. for 0 minute or30 minutes in the presence of 1 mmol/L NADPH in 0.2 mL of a buffer (50mmol/L Tris-HCl pH 7.4, 150 mmol/L potassium chloride, 10 mmol/Lmagnesium chloride) containing 0.5 mg protein/mL of human livermicrosomes. After the reaction, 50 μL of the reaction solution was addedto 100 μL of a methanol/acetonitrile=1/1 (v/v), mixed and centrifuged at3000 rpm for 15 minutes. The test compound in the supernatant wasquantified by LC/MS/MS, and a remaining amount of the test compoundafter the reaction was calculated, letting a compound amount at 0 minutereaction time to be 100%.

BA Test

Materials and methods for studies on oral absorption

(1) Animals: SD Rats

(2) Animal Husbandry:

Rats had free access to solid food and sterilized bottled tap water.

(3) Setting of Dose and Group Compositions:

orally or intravenously administered at a predetermined dose; Groupcompositions were as shown below (Dose depends on the compound)

Oral: 1 to 30 mg/kg (n=2 to 3)

Intravenous: 0.5 to 10 mg/kg (n=2 to 3)

(4) Preparation for Dosing Formulation:

for oral administration, in a solution or a suspension state; forintravenous administration, in a solubilized state

(5) Dosing Procedure:

In oral administration study, the test suspension was dosed to thestomach of rats by using a gavage tube In intravenous administrationstudy, the test solution was dosed to rats via tail vein using a syringewith a needle.

(6) Evaluation Items:

Blood was collected at each time point, and plasma concentration of thetest substance was determined by a LC/MS/MS system.

(7) Data Analysis:

Regarding the transition of the plasma concentration, area under theplasma concentration-time curve (AUC) was calculated by means ofWinNonlin® program, respectively. Bioavailability (BA) was calculated byusing AUC values in oral administration study and in intravenousadministration study.

Formulation Example 1

A hard gelatin capsule is prepared by using the following ingredients:

Dose (mg/capsule) Active ingredient 250 Starch (dry) 200 Magnesiumstearate 10 Total 460 mg

Formulation Example 2

A tablet is prepared by using the following ingredients:

Dose (mg/tablet) Active ingredient 250 Cellulose (microcrystal) 400Silicon dioxide (fumed) 10 Stearic acid 5 Total 665 mg

The ingredients are mixed, and compressed to form tables each weighing665 mg.

Formulation Example 3

An aerosol solution containing the following ingredients is prepared:

Weight Active ingredient 0.25 Ethanol 25.75 Propellant 22(chlorodifluoromethane) 74.00 Total 100.00

The active ingredient and ethanol are mixed, and the mixture is added topart of propellant 22, cooled to −30° C., and transferred to a packingmachine. Then, a necessary amount is supplied to a stainless steelcontainer, and diluted with the remaining propellant. A bubble unit isattached to the container.

Formulation Example 4

A tablet containing 60 mg of the active ingredient is prepared in thefollowing manner:

Active ingredient 60 mg Starch 45 mg Microcrystalline cellulose 35 mgPolyvinylpyrrolidone (10% solution in water) 4 mg Sodium carboxymethylstarch 4.5 mg Magnesium stearate 0.5 mg Talc 1 mg Total 150 mg

The active ingredient, starch, and cellulose are passed through a No. 45mesh U.S. sieve and mixed thoroughly. An aqueous solution containingpolyvinylpyrrolidone is mixed with obtained powder and then the mixtureis passed through a No. 14 mesh U.S. sieve. Granules obtained in thismanner are dried at 50° C. and passed through a No. 18 mesh U.S. sieve.The sodium carboxymethyl starch, magnesium stearate and talc that arepassed through a No. 60 mesh U.S. sieve in advance, are added to thegranules, mixed, and then compressed by a tableting machine to obtaintablets each weighing 150 mg.

Formulation Example 5

A capsule containing 80 mg of the active ingredient is prepared in thefollowing manner:

Active ingredient 80 mg Starch 59 mg Microcrystalline cellulose 59 mgMagnesium stearate 2 mg Total 200 mg

The active ingredient, starch, cellulose, and magnesium stearate aremixed, and passed through a No. 45 mesh U.S. sieve, and filled into ahard gelatin capsule in 200 mg quantities.

Formulation Example 6

Suppository containing 225 mg of the active ingredient is prepared inthe following manner:

Active ingredient 225 mg Saturated fatty acid glyceride 2000 mg Total2225 mg

The active ingredient is passed through a No. 60 mesh U.S. sieve, andsuspended in saturated fatty acid glyceride that is melted by heatingleast necessarily in advance. Then, the resultant mixture is put into anapparent 2 g mold, and cooled.

Formulation Example 7

A suspension containing 50 mg of the active ingredient is prepared inthe following manner:

Active ingredient 50 mg Sodium carboxymethyl cellulose 50 mg Syrup 1.25mL Benzoic acid solution 0.10 mL Flavor q.v. Pigment q.v. Purified waterto total 5 mL

The active ingredient is passed through a No. 45 mesh U.S. sieve, andmixed with sodium carboxymethyl cellulose and syrup to form a smoothpaste. The benzoic acid solution and the flavor diluted with part ofwater are added, and stirred. Then a sufficient amount of water is addedto achieve required volume.

Formulation Example 8

An intravenous formulation is prepared in the following manner:

Active ingredient 100 mg Saturated fatty acid glyceride 1000 mL

The solution of the above ingredients is intravenously administered to apatient usually at a speed of 1 mL per minute.

INDUSTRIAL APPLICABILITY

As is apparent from the above test examples, the compounds according tothe present invention show inhibitory activity on endothelial lipase.Therefore, the compounds according to the present invention are veryuseful as therapeutic agents for lipid metabolism abnormality,hyperlipidemia or arteriosclerosis.

1. A pharmaceutical composition having inhibitory activity onendothelial lipase, comprising a compound represented by formula (I):

its pharmaceutically acceptable salt, or a solvate thereof, wherein RingA is nitrogen-containing hetero ring, Ring A is optionally substitutedwith a substituent other than a group represented by the formula:—C(R¹R²)—C(═O)—NR³R⁴ and a group represented by the formula: —R⁵, abroken line represents the presence or absence of a bond, Z is —NR⁶—,═N—, —O—, or —S—, R⁶ is hydrogen, substituted or unsubstituted alkyl,substituted or unsubstituted alkenyl, substituted or unsubstitutedalkynyl, substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl, or substituted or unsubstituted heterocycle,R¹ and R² are each independently hydrogen, halogen, cyano, nitro,carboxy, or substituted or unsubstituted alkyl, R³ is hydrogen orsubstituted or unsubstituted alkyl, R⁴ is hydrogen, substituted orunsubstituted alkyl, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedheterocycle, or substituted or unsubstituted amino, or R³ and R⁴ takentogether with the adjacent nitrogen atom to which they are attached forma substituted or unsubstituted ring, R⁵ is hydrogen, halogen, hydroxy,cyano, nitro, carboxy, substituted or unsubstituted alkyl, substitutedor unsubstituted alkenyl, substituted or unsubstituted alkynyl,substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl, substituted or unsubstituted heterocycle,substituted or unsubstituted alkyloxy, substituted or unsubstitutedaryloxy, substituted or unsubstituted heteroaryloxy, substituted orunsubstituted cycloalkyloxy, substituted or unsubstitutedcycloalkenyloxy, substituted or unsubstituted heterocycleoxy,substituted or unsubstituted alkylthio, substituted or unsubstitutedarylthio, substituted or unsubstituted heteroarylthio, substituted orunsubstituted cycloalkylthio, substituted or unsubstitutedcycloalkenylthio, substituted or unsubstituted heterocyclethio,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedarylsulfonyl, substituted or unsubstituted heteroarylsulfonyl,substituted or unsubstituted cycloalkylsulfonyl, substituted orunsubstituted cycloalkenylsulfonyl, substituted or unsubstitutedheterocyclesulfonyl, substituted or unsubstituted acyl, substituted orunsubstituted carbamoyl, or substituted or unsubstituted amino, with theproviso that compounds wherein Ring A is thiazolopyrimidine and R³ andR⁴ taken together with the adjacent nitrogen atom to which they areattached optionally form a substituted or unsubstituted ring areexcluded.
 2. The pharmaceutical composition of claim 1, itspharmaceutically acceptable salt, or a solvate thereof, wherein Z is—S—.
 3. The pharmaceutical composition of claim 1, its pharmaceuticallyacceptable salt, or a solvate thereof, wherein Ring A is monocyclicnitrogen-containing aromatic hetero ring.
 4. The pharmaceuticalcomposition of claim 1, its pharmaceutically acceptable salt, or asolvate thereof, wherein Ring A is bicyclic nitrogen-containing aromatichetero ring.
 5. The pharmaceutical composition of claim 1, itspharmaceutically acceptable salt, or a solvate thereof, wherein R⁵ issubstituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl, substituted or unsubstituted heterocycle,substituted or unsubstituted aryloxy, substituted or unsubstitutedheteroaryloxy, substituted or unsubstituted cycloalkyloxy, substitutedor unsubstituted cycloalkenyloxy, substituted or unsubstitutedheterocycleoxy, substituted or unsubstituted arylthio, substituted orunsubstituted heteroarylthio, substituted or unsubstitutedcycloalkylthio, substituted or unsubstituted cycloalkenylthio,substituted or unsubstituted heterocyclethio, substituted orunsubstituted arylsulfonyl, substituted or unsubstitutedheteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl,substituted or unsubstituted cycloalkenylsulfonyl, substituted orunsubstituted heterocyclesulfonyl, or substituted or unsubstitutedamino.
 6. The pharmaceutical composition of claim 1, itspharmaceutically acceptable salt, or a solvate thereof, wherein R⁵ issubstituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted aryloxy, substituted orunsubstituted heteroaryloxy, substituted or unsubstituted arylthio,substituted or unsubstituted heteroarylthio, substituted orunsubstituted arylsulfonyl, substituted or unsubstitutedheteroarylsulfonyl, or substituted or unsubstituted amino.
 7. Thepharmaceutical composition of claim 1, its pharmaceutically acceptablesalt, or a solvate thereof, wherein R⁴ is substituted or unsubstitutedalkyl, which is a substituted or unsubstituted arylalkyl, or substitutedor unsubstituted heteroarylalkyl.
 8. A compound represented by formula(II):

its pharmaceutically acceptable salt, or a solvate thereof, wherein Z¹is —O— or —S—, Ring B is aromatic carbocycle, aromatic hetero ring,nonaromatic carbocycle, or nonaromatic hetero ring, R¹ and R² are eachindependently hydrogen, halogen, cyano, nitro, carboxy, or substitutedor unsubstituted alkyl, R³ is hydrogen or substituted or unsubstitutedalkyl, R^(4a) is substituted or unsubstituted arylalkyl, substituted orunsubstituted heteroarylalkyl, substituted or unsubstitutedcycloalkylalkyl, substituted or unsubstituted cycloalkenylalkyl,substituted or unsubstituted heterocyclealkyl, a group represented bythe formula: —(CR⁷R⁸)n-C(═O)—R⁹, wherein R⁷ and R⁸ are eachindependently hydrogen, halogen, hydroxy, carboxy, substituted orunsubstituted alkyl, substituted or unsubstituted alkyloxy, substitutedor unsubstituted aryl, substituted or unsubstituted heteroaryl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedcycloalkenyl or substituted or unsubstituted heterocycle, n is aninteger of 1 to 10, R⁹ is —OR¹⁰ or —NR¹¹R¹², R¹⁰ is hydrogen,substituted or unsubstituted alkyl, substituted or unsubstituted aryl,substituted or unsubstituted heteroaryl, substituted or unsubstitutedcycloalkyl, substituted or unsubstituted cycloalkenyl or substituted orunsubstituted heterocycle, R¹¹ and R¹² are each independently hydrogen,substituted or unsubstituted alkyl, substituted or unsubstitutedalkyloxy, substituted or unsubstituted aryloxy, substituted orunsubstituted heteroaryloxy, substituted or unsubstituted alkylsulfonyl,substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl or substituted or unsubstituted heterocycleor a group represented by the formula: —C(R⁷R⁸)n-O—R¹³, wherein R⁷, R⁸and n are as defined in the above, R¹³ is hydrogen or substituted orunsubstituted alkyl, or R³ and R^(4a) taken together with the adjacentnitrogen atom to which they are attached form a substituted orunsubstituted ring, R⁵ is hydrogen, halogen, hydroxy, cyano, nitro,carboxy, substituted or unsubstituted alkyl, substituted orunsubstituted alkenyl, substituted or unsubstituted alkynyl, substitutedor unsubstituted aryl, substituted or unsubstituted heteroaryl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedcycloalkenyl, substituted or unsubstituted heterocycle, substituted orunsubstituted alkyloxy, substituted or unsubstituted aryloxy,substituted or unsubstituted heteroaryloxy, substituted or unsubstitutedcycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substitutedor unsubstituted heterocycleoxy, substituted or unsubstituted alkylthio,substituted or unsubstituted arylthio, substituted or unsubstitutedheteroarylthio, substituted or unsubstituted cycloalkylthio, substitutedor unsubstituted cycloalkenylthio, substituted or unsubstitutedheterocyclethio, substituted or unsubstituted alkylsulfonyl, substitutedor unsubstituted arylsulfonyl, substituted or unsubstitutedheteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl,substituted or unsubstituted cycloalkenylsulfonyl, substituted orunsubstituted heterocyclesulfonyl, substituted or unsubstituted acyl,substituted or unsubstituted carbamoyl, or substituted or unsubstitutedamino, R^(X) is halogen, hydroxy, cyano, nitro, carboxy, substituted orunsubstituted alkyl, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkyloxy, substituted orunsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted cycloalkyloxy, substituted or unsubstitutedcycloalkenyloxy, substituted or unsubstituted heterocycleoxy,substituted or unsubstituted alkylthio, substituted or unsubstitutedarylthio, substituted or unsubstituted heteroarylthio, substituted orunsubstituted cycloalkylthio, substituted or unsubstitutedcycloalkenylthio, substituted or unsubstituted heterocyclethio,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedarylsulfonyl, substituted or unsubstituted heteroarylsulfonyl,substituted or unsubstituted cycloalkylsulfonyl, substituted orunsubstituted cycloalkenylsulfonyl, substituted or unsubstitutedheterocyclesulfonyl, substituted or unsubstituted acyl, substituted orunsubstituted carbamoyl or substituted or unsubstituted amino, m is aninteger of 0 to 3, with the proviso that compounds, wherein Z¹ is —S—,Ring B is pyrimidine and R³ and R^(4a) taken together with the adjacentnitrogen atom to which they are attached optionally form a substitutedor unsubstituted ring, compounds, wherein Z¹ is —O—, Ring B is benzene,R⁵ is methyl, m is 0 and R³ and R^(4a) taken together with the adjacentnitrogen atom to which they are attached optionally form a substitutedor unsubstituted ring, compounds, wherein Z¹ is —O—, Ring B is benzene,R⁵ is hydrogen, m is 1, R^(X) is methyl, and R³ and R^(4a) takentogether with the adjacent nitrogen atom to which they are attachedoptionally form a substituted or unsubstituted ring and the compoundsshown as follows are excluded:


9. The compound of claim 8, its pharmaceutically acceptable salt, or asolvate thereof, wherein Z¹ is —S—.
 10. The compound of claim 8, itspharmaceutically acceptable salt, or a solvate thereof, wherein Ring Bis aromatic carbocycle.
 11. The compound of claim 8, itspharmaceutically acceptable salt, or a solvate thereof, wherein Ring Bis benzene.
 12. The compound of claim 8, its pharmaceutically acceptablesalt, or a solvate thereof, wherein Ring B is monocyclic aromatic heteroring.
 13. The compound of claim 9, its pharmaceutically acceptable salt,or a solvate thereof, wherein the compound represented by formula (II)is a compound represented by formula (III):

wherein X and Y are each independently —CR^(X)═, —CH═, or —N═, and R^(Y)is hydrogen or R^(X).
 14. The compound of claim 9, its pharmaceuticallyacceptable salt, or a solvate thereof, wherein the compound representedby formula (II) is a compound represented by formula (IV):

wherein X and Y are each independently —CR^(X)═, —CH═, or —N═, and R^(Y)is hydrogen or R^(X).
 15. The compound of claim 13, its pharmaceuticallyacceptable salt, or a solvate thereof, wherein X and Y are eachindependently —CR^(X)═ or —CH═.
 16. The compound of claim 8, itspharmaceutically acceptable salt, or a solvate thereof, wherein R^(4a)is substituted or unsubstituted arylalkyl or substituted orunsubstituted heteroarylalkyl.
 17. The compound of claim 8, itspharmaceutically acceptable salt, or a solvate thereof, wherein R^(4a)is substituted or unsubstituted arylalkyl.
 18. The compound of claim 8,its pharmaceutically acceptable salt, or a solvate thereof, whereinR^(4a) is

wherein R^(a) is halogen, hydroxy, carboxy, nitro, cyano, azide,substituted or unsubstituted alkyl, substituted or unsubstitutedalkenyl, substituted or unsubstituted alkynyl, substituted orunsubstituted aryl, substituted or unsubstituted cycloalkyl, substitutedor unsubstituted cycloalkenyl, substituted or unsubstituted heteroaryl,substituted or unsubstituted heterocycle, substituted or unsubstitutedalkyloxy, substituted or unsubstituted aryloxy, substituted orunsubstituted silyloxy, substituted or unsubstituted amino, substitutedor unsubstituted carbamoyl, substituted or unsubstituted carbamoyloxy,substituted or unsubstituted acyl, substituted or unsubstitutedalkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted orunsubstituted sulfamoyl, or substituted or unsubstitutedalkyloxycarbonyl, R¹⁴ and R¹⁵ are each independently hydrogen, halogen,hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl,substituted or unsubstituted alkenyl, or substituted or unsubstitutedalkynyl, and b is an integer of 0 to
 3. 19. The compound of claim 18,its pharmaceutically acceptable salt, or a solvate thereof, whereinR^(4a) is

wherein c is an integer of 0 to
 2. 20. The compound of claim 8, itspharmaceutically acceptable salt, or a solvate thereof, wherein R^(4a)is a group represented by the formula: —(CR⁷R⁸)n-C(═O)—R⁹.
 21. Thecompound of claim 20, its pharmaceutically acceptable salt, or a solvatethereof, wherein R⁹ is —OR¹⁰.
 22. The compound of claim 20, itspharmaceutically acceptable salt, or a solvate thereof, wherein R⁹ is—NR¹¹R¹².
 23. The compound of claim 22, its pharmaceutically acceptablesalt, or a solvate thereof, wherein R¹² is substituted or unsubstitutedalkyl.
 24. The compound of claim 22, its pharmaceutically acceptablesalt, or a solvate thereof, wherein R¹¹ is hydrogen.
 25. The compound ofclaim 20, its pharmaceutically acceptable salt, or a solvate thereof,wherein n is
 1. 26. The compound of claim 20, its pharmaceuticallyacceptable salt, or a solvate thereof, wherein R⁷ and R⁸ are hydrogen.27. The compound of claim 8, its pharmaceutically acceptable salt, or asolvate thereof, wherein R¹ and R² are hydrogen.
 28. The compound ofclaim 8, its pharmaceutically acceptable salt, or a solvate thereof,wherein R³ is hydrogen.
 29. The compound of claim 8, itspharmaceutically acceptable salt, or a solvate thereof, wherein R⁵ issubstituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl, substituted or unsubstituted heterocycle,substituted or unsubstituted aryloxy, substituted or unsubstitutedheteroaryloxy, substituted or unsubstituted cycloalkyloxy, substitutedor unsubstituted cycloalkenyloxy, substituted or unsubstitutedheterocycleoxy, substituted or unsubstituted arylthio, substituted orunsubstituted heteroarylthio, substituted or unsubstitutedcycloalkylthio, substituted or unsubstituted cycloalkenylthio,substituted or unsubstituted heterocyclethio, substituted orunsubstituted arylsulfonyl, substituted or unsubstitutedheteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl,substituted or unsubstituted cycloalkenylsulfonyl, substituted orunsubstituted heterocyclesulfonyl, or substituted or unsubstitutedamino.
 30. The compound of claim 8, its pharmaceutically acceptablesalt, or a solvate thereof, wherein R⁵ is substituted or unsubstitutedaryl, substituted or unsubstituted heteroaryl, substituted orunsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted arylthio, substituted or unsubstitutedheteroarylthio, substituted or unsubstituted arylsulfonyl, substitutedor unsubstituted heteroarylsulfonyl, or substituted or unsubstitutedamino.
 31. The compound of claim 8, its pharmaceutically acceptablesalt, or a solvate thereof, wherein R⁵ is hydrogen, substituted orunsubstituted alkyl, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted heterocycle, substituted or unsubstitutedalkyloxy, substituted or unsubstituted aryloxy, substituted orunsubstituted arylsulfonyl, or substituted or unsubstituted acyl.
 32. Acompound represented by formula (V):

its pharmaceutically acceptable salt, or a solvate thereof, wherein RingC is monocyclic or bicyclic hetero ring, R^(4b) is substitutedarylalkyl, wherein a substituent on a ring of the substituted arylalkylis carboxy, substituted or unsubstituted carbamoyl, substituted orunsubstituted alkylsulfonyl or substituted or unsubstituted sulfamoyl,substituted heteroarylalkyl, wherein a substituent on a ring of thesubstituted heteroarylalkyl is carboxy, substituted or unsubstitutedcarbamoyl, substituted or unsubstituted alkylsulfonyl or substituted orunsubstituted sulfamoyl, substituted cycloalkylalkyl, wherein asubstituent on a ring of the substituted cycloalkylalkyl is carboxy,substituted or unsubstituted carbamoyl, substituted or unsubstitutedalkylsulfonyl or substituted or unsubstituted sulfamoyl, substitutedcycloalkenylalkyl, wherein a substituent on a ring of the substitutedcycloalkenylalkyl is carboxy, substituted or unsubstituted carbamoyl,substituted or unsubstituted alkylsulfonyl or substituted orunsubstituted sulfamoyl, substituted heterocyclealkyl, wherein asubstituent on a ring of the substituted heterocyclealkyl is carboxy,substituted or unsubstituted carbamoyl, substituted or unsubstitutedalkylsulfonyl, or substituted or unsubstituted sulfamoyl, or a grouprepresented by the formula: —(CR⁷R⁸)n-C(═O)—R⁹, wherein R⁷ and R⁸ areeach independently hydrogen, halogen, hydroxy, carboxy, substituted orunsubstituted alkyl, substituted or unsubstituted alkyloxy, substitutedor unsubstituted aryl, substituted or unsubstituted heteroaryl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedcycloalkenyl or substituted or unsubstituted heterocycle, n is aninteger of 1 to 10, R⁹ is —OR¹⁰ or —NR¹¹R¹², R¹⁰ is hydrogen,substituted or unsubstituted alkyl, substituted or unsubstituted aryl,substituted or unsubstituted heteroaryl, substituted or unsubstitutedcycloalkyl, substituted or unsubstituted cycloalkenyl or substituted orunsubstituted heterocycle, R¹¹ and R¹² are each independently hydrogen,substituted or unsubstituted alkyl, substituted or unsubstitutedalkyloxy, substituted or unsubstituted aryloxy, substituted orunsubstituted heteroaryloxy, substituted or unsubstituted alkylsulfonyl,substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl, or substituted or unsubstituted heterocycle,R⁵ is hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted orunsubstituted alkyl, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkyloxy, substituted orunsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted cycloalkyloxy, substituted or unsubstitutedcycloalkenyloxy, substituted or unsubstituted heterocycleoxy,substituted or unsubstituted alkylthio, substituted or unsubstitutedarylthio, substituted or unsubstituted heteroarylthio, substituted orunsubstituted cycloalkylthio, substituted or unsubstitutedcycloalkenylthio, substituted or unsubstituted heterocyclethio,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedarylsulfonyl, substituted or unsubstituted heteroarylsulfonyl,substituted or unsubstituted cycloalkylsulfonyl, substituted orunsubstituted cycloalkenylsulfonyl, substituted or unsubstitutedheterocyclesulfonyl, substituted or unsubstituted acyl, substituted orunsubstituted carbamoyl, or substituted or unsubstituted amino, R^(X) ishalogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstitutedalkyl, substituted or unsubstituted alkenyl, substituted orunsubstituted alkynyl, substituted or unsubstituted aryl, substituted orunsubstituted heteroaryl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkyloxy, substituted orunsubstituted aryloxy, substituted or unsubstituted heteroaryloxy,substituted or unsubstituted cycloalkyloxy, substituted or unsubstitutedcycloalkenyloxy, substituted or unsubstituted heterocycleoxy,substituted or unsubstituted alkylthio, substituted or unsubstitutedarylthio, substituted or unsubstituted heteroarylthio, substituted orunsubstituted cycloalkylthio, substituted or unsubstitutedcycloalkenylthio, substituted or unsubstituted heterocyclethio,substituted or unsubstituted alkylsulfonyl, substituted or unsubstitutedarylsulfonyl, substituted or unsubstituted heteroarylsulfonyl,substituted or unsubstituted cycloalkylsulfonyl, substituted orunsubstituted cycloalkenylsulfonyl, substituted or unsubstitutedheterocyclesulfonyl, substituted or unsubstituted acyl, substituted orunsubstituted carbamoyl, or substituted or unsubstituted amino, m is aninteger of 0 to 3, with the proviso that compounds:

are excluded.
 33. The compound of claim 32, its pharmaceuticallyacceptable salt, or a solvate thereof, wherein Ring C is bicycle.
 34. Apharmaceutical composition, comprising the compound of claim 8, itspharmaceutically acceptable salt, or a solvate thereof.
 35. Apharmaceutical composition, comprising the compound of claim 8, itspharmaceutically acceptable salt, or a solvate thereof, which has aninhibitory activity on endothelial lipase.